Skip to main content
SpringerLink
Log in

The Scribble–Dlg–Lgl Module in Cell Polarity Regulation

  • Chapter
  • First Online:
Cell Polarity 1

Abstract

Although the Scribble polarity module has long been known as a key regulator of apicobasal polarity, it is only recently that its broader role in the control of near all polarity states and transitions is being appreciated. Here we review the Scribble module in the regulation of cell polarity and other cellular functions at the molecular and cellular level. The more recent detailed analysis of multiple vertebrate models for each of its component homologues, Scribble, Dlg and Lgl, has revealed specific but also common roles for individual homologues in a variety of developmental contexts. In addition, emerging data has also implicated the Scribble polarity module in human developmental syndromes and the etiology of human cancer, highlighting a need for a better understanding of this polarity module for therapeutic purposes. Unlocking the temporal and spatial coordination of the myriad interactions that these signaling scaffolds regulate is a major challenge for the field and will be key to resolve the function of Scribble, Dlg, and Lgl in the control of cell polarity and tissue architecture.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adey NB, Huang L, Ormonde PA, Baumgard ML, Pero R, Byreddy DV, Tavtigian SV, Bartel PL (2000) Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain both inhibits and stimulates PDZ binding. Cancer Res 60(1):35–37

    CAS  PubMed  Google Scholar 

  • Albertson R, Doe CQ (2003) Dlg, Scrib and Lgl regulate neuroblast cell size and mitotic spindle asymmetry. Nat Cell Biol 5(2):166–170. doi:10.1038/ncb922

    CAS  PubMed  Google Scholar 

  • Amoyel M, Bach EA (2014) Cell competition: how to eliminate your neighbours. Development 141(5):988–1000. doi:10.1242/dev.079129, 141/5/988 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Armenti ST, Nance J (2012) Adherens junctions in C. elegans embryonic morphogenesis. Subcell Biochem 60:279–299. doi:10.1007/978-94-007-4186-7_12

    PubMed Central  CAS  PubMed  Google Scholar 

  • Arnaud C, Sebbagh M, Nola S, Audebert S, Bidaut G, Hermant A, Gayet O, Dusetti NJ, Ollendorff V, Santoni MJ, Borg JP, Lecine P (2009) MCC, a new interacting protein for Scrib, is required for cell migration in epithelial cells. FEBS Lett 583(14):2326–2332

    CAS  PubMed  Google Scholar 

  • Arquier N, Perrin L, Manfruelli P, Semeriva M (2001) The Drosophila tumor suppressor gene lethal(2)giant larvae is required for the emission of the Decapentaplegic signal. Development 128(12):2209–2220

    CAS  PubMed  Google Scholar 

  • Atwood SX, Prehoda KE (2009) aPKC phosphorylates Miranda to polarize fate determinants during neuroblast asymmetric cell division. Curr Biol 19(9):723–729. doi:10.1016/j.cub.2009.03.056, S0960-9822(09)00910-5 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Audebert S, Navarro C, Nourry C, Chasserot-Golaz S, Lecine P, Bellaiche Y, Dupont JL, Premont RT, Sempere C, Strub JM, Van Dorsselaer A, Vitale N, Borg JP (2004) Mammalian Scribble forms a tight complex with the betaPIX exchange factor. Curr Biol 14(11):987–995

    CAS  PubMed  Google Scholar 

  • Bahri S, Wang S, Conder R, Choy J, Vlachos S, Dong K, Merino C, Sigrist S, Molnar C, Yang X, Manser E, Harden N (2010) The leading edge during dorsal closure as a model for epithelial plasticity: Pak is required for recruitment of the Scribble complex and septate junction formation. Development 137(12):2023–2032. doi:10.1242/dev.045088

    CAS  PubMed  Google Scholar 

  • Banks L, Pim D, Thomas M (2012) Human tumour viruses and the deregulation of cell polarity in cancer. Nat Rev Cancer 12(12):877–886. doi:10.1038/nrc3400

    CAS  PubMed  Google Scholar 

  • Baron M (2012) Endocytic routes to Notch activation. Semin Cell Dev Biol 23(4):437–442. doi:10.1016/j.semcdb.2012.01.008, S1084-9521(12)00012-2 [pii]

    CAS  PubMed  Google Scholar 

  • Beatty A, Morton D, Kemphues K (2010) The C. elegans homolog of Drosophila Lethal giant larvae functions redundantly with PAR-2 to maintain polarity in the early embryo. Development 137(23):3995–4004. doi:10.1242/dev.056028, dev.056028 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Belotti E, Polanowska J, Daulat AM, Audebert S, Thome V, Lissitzky JC, Lembo F, Biblek K, Omi S, Lenfant N, Gangar A, Montcouquiol M, Santoni MJ, Sebbagh M, Aurrand-Lions M, Angers S, Kodjabachian L, Reboul J, Borg JP (2013) The human PDZome: a gateway to PDZ mediated functions. Mol Cell Proteomics. doi:10.1074/mcp.O112.021022

    PubMed Central  PubMed  Google Scholar 

  • Bergstralh DT, Lovegrove HE, St Johnston D (2013) Curr Biol 23:1707–1712

    PubMed Central  CAS  PubMed  Google Scholar 

  • Betschinger J, Eisenhaber F, Knoblich JA (2005) Phosphorylation-induced autoinhibition regulates the cytoskeletal protein Lethal (2) giant larvae. Curr Biol 15(3):276–282

    CAS  PubMed  Google Scholar 

  • Bilder D (2004) Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors. Genes Dev 18(16):1909–1925

    CAS  PubMed  Google Scholar 

  • Bilder D, Li M, Perrimon N (2000) Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science 289(5476):113–116

    CAS  PubMed  Google Scholar 

  • Bilder D, Perrimon N (2000) Localization of apical epithelial determinants by the basolateral PDZ protein Scribble. Nature 403(6770):676–680

    CAS  PubMed  Google Scholar 

  • Blankenship JT, Fuller MT, Zallen JA (2007) The Drosophila homolog of the Exo84 exocyst subunit promotes apical epithelial identity. J Cell Sci 120(Pt 17):3099–3110

    CAS  PubMed  Google Scholar 

  • Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (2004) A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat Cell Biol 6(2):97–105. doi:10.1038/ncb1086, ncb1086 [pii]

    CAS  PubMed  Google Scholar 

  • Brooks SP, Coccia M, Tang HR, Kanuga N, Machesky LM, Bailly M, Cheetham ME, Hardcastle AJ (2010) The Nance-Horan syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology. Hum Mol Genet 19(12):2421–2432. doi:10.1093/hmg/ddq125, dq125 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Brumby AM, Richardson HE (2003) Scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J 22(21):5769–5779

    PubMed Central  CAS  PubMed  Google Scholar 

  • Buchsbaum RJ, Connolly BA, Feig LA (2002) Interaction of Rac exchange factors Tiam1 and Ras-GRF1 with a scaffold for the p38 mitogen-activated protein kinase cascade. Mol Cell Biol 22(12):4073–4085

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bunney TD, Katan M (2010) Phosphoinositide signalling in cancer: beyond PI3K and PTEN. Nat Rev Cancer 10(5):342–352. doi:10.1038/nrc2842, nrc2842 [pii]

    CAS  PubMed  Google Scholar 

  • Caddy J, Wilanowski T, Darido C, Dworkin S, Ting SB, Zhao Q, Rank G, Auden A, Srivastava S, Papenfuss TA, Murdoch JN, Humbert PO, Parekh V, Boulos N, Weber T, Zuo J, Cunningham JM, Jane SM (2010) Epidermal wound repair is regulated by the planar cell polarity signaling pathway. Dev Cell 19(1):138–147. doi:10.1016/j.devcel.2010.06.008, S1534-5807(10)00298-4 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Caruana G, Bernstein A (2001) Craniofacial dysmorphogenesis including cleft palate in mice with an insertional mutation in the discs large gene. Mol Cell Biol 21(5):1475–1483

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chang JT, Ciocca ML, Kinjyo I, Palanivel VR, McClurkin CE, Dejong CS, Mooney EC, Kim JS, Steinel NC, Oliaro J, Yin CC, Florea BI, Overkleeft HS, Berg LJ, Russell SM, Koretzky GA, Jordan MS, Reiner SL (2011) Asymmetric proteasome segregation as a mechanism for unequal partitioning of the transcription factor T-bet during T lymphocyte division. Immunity 34(4):492–504. doi:10.1016/j.immuni.2011.03.017, S1074-7613(11)00125-7 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chang JT, Palanivel VR, Kinjyo I, Schambach F, Intlekofer AM, Banerjee A, Longworth SA, Vinup KE, Mrass P, Oliaro J, Killeen N, Orange JS, Russell SM, Weninger W, Reiner SL (2007) Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315(5819):1687–1691. doi:10.1126/science.1139393

    CAS  PubMed  Google Scholar 

  • Chen CL, Schroeder MC, Kango-Singh M, Tao C, Halder G (2012) Tumor suppression by cell competition through regulation of the Hippo pathway. Proc Natl Acad Sci U S A 109(2):484–489. doi:10.1073/pnas.1113882109, 1113882109 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chen X, Macara IG (2005) Par-3 controls tight junction assembly through the Rac exchange factor Tiam1. Nat Cell Biol 7(3):262–269

    CAS  PubMed  Google Scholar 

  • Cho KO, Hunt CA, Kennedy MB (1992) The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein. Neuron 9(5):929–942

    CAS  PubMed  Google Scholar 

  • Clark BS, Cui S, Miesfeld JB, Klezovitch O, Vasioukhin V, Link BA (2012) Loss of Llgl1 in retinal neuroepithelia reveals links between apical domain size, Notch activity and neurogenesis. Development 139(9):1599–1610. doi:10.1242/dev.078097

    PubMed Central  CAS  PubMed  Google Scholar 

  • Claveria C, Giovinazzo G, Sierra R, Torres M (2013) Myc-driven endogenous cell competition in the early mammalian embryo. Nature 500:39–44

    CAS  PubMed  Google Scholar 

  • Clevers H, Nusse R (2012) Wnt/beta-catenin signaling and disease. Cell 149(6):1192–1205. doi:10.1016/j.cell.2012.05.012, S0092-8674(12)00586-7 [pii]

    CAS  PubMed  Google Scholar 

  • Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, Inui M, Montagner M, Parenti AR, Poletti A, Daidone MG, Dupont S, Basso G, Bicciato S, Piccolo S (2011) The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 147(4):759–772. doi:10.1016/j.cell.2011.09.048, S0092-8674(11)01218-9 [pii]

    CAS  PubMed  Google Scholar 

  • Cordero JB, Macagno JP, Stefanatos RK, Strathdee KE, Cagan RL, Vidal M (2010) Oncogenic Ras diverts a host TNF tumor suppressor activity into tumor promoter. Dev Cell 18(6):999–1011

    PubMed Central  CAS  PubMed  Google Scholar 

  • Courbard JR, Djiane A, Wu J, Mlodzik M (2009) The apical/basal-polarity determinant Scribble cooperates with the PCP core factor Stbm/Vang and functions as one of its effectors. Dev Biol 333(1):67–77. doi:10.1016/j.ydbio.2009.06.024, S0012-1606(09)00993-2 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cuthbert PC, Stanford LE, Coba MP, Ainge JA, Fink AE, Opazo P, Delgado JY, Komiyama NH, O’Dell TJ, Grant SG (2007) Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies. J Neurosci 27(10):2673–2682. doi:10.1523/JNEUROSCI.4457-06.2007

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dahan I, Petrov D, Cohen-Kfir E, Ravid S (2014) The tumor suppressor Lgl1 forms discrete complexes with NMII-A and Par6alpha-aPKCzeta that are affected by Lgl1 phosphorylation. J Cell Sci 127(Pt 2):295–304. doi:10.1242/jcs.127357, jcs.127357 [pii]

    CAS  PubMed  Google Scholar 

  • Dahan I, Yearim A, Touboul Y, Ravid S (2012) The tumor suppressor Lgl1 regulates NMII-A cellular distribution and focal adhesion morphology to optimize cell migration. Mol Biol Cell. doi:10.1091/mbc.E11-01-0015, mbc.E11-01-0015 [pii]

    PubMed Central  PubMed  Google Scholar 

  • de Beco S, Ziosi M, Johnston LA (2012) New frontiers in cell competition. Dev Dyn 241(5):831–841. doi:10.1002/dvdy.23783

    PubMed Central  PubMed  Google Scholar 

  • de Vreede G, Schoenfeld JD, Windler SL, Morrison H, Lu H, Bilder D (2014) The Scribble module regulates retromer-dependent endocytic trafficking during epithelial polarization. Development 141(14):2796–2802. doi:10.1242/dev.105403, 141/14/2796 [pii]

    PubMed  Google Scholar 

  • Doggett K, Grusche FA, Richardson HE, Brumby AM (2011) Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo pathway signaling. BMC Dev Biol 11:57. doi:10.1186/1471-213X-11-57, 1471-213X-11-57 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dollar GL, Weber U, Mlodzik M, Sokol SY (2005) Regulation of Lethal giant larvae by Dishevelled. Nature 437(7063):1376–1380

    CAS  PubMed  Google Scholar 

  • Dow LE, Elsum IA, King CL, Kinross KM, Richardson HE, Humbert PO (2008) Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling. Oncogene 27(46):5988–6001. doi:10.1038/onc.2008.219, onc2008219 [pii]

    CAS  PubMed  Google Scholar 

  • Dow LE, Humbert PO (2007) Polarity regulators and the control of epithelial architecture, cell migration, and tumorigenesis. Int Rev Cytol 262:253–302

    CAS  PubMed  Google Scholar 

  • Dow LE, Kauffman JS, Caddy J, Zarbalis K, Peterson AS, Jane SM, Russell SM, Humbert PO (2007) The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge. Oncogene 26(16):2272–2282. doi:10.1038/sj.onc.1210016

    CAS  PubMed  Google Scholar 

  • Eastburn DJ, Zegers MM, Mostov KE (2012) Scrib regulates HGF-mediated epithelial morphogenesis and is stabilized by Sgt1-HSP90. J Cell Sci 125(Pt 17):4147–4157. doi:10.1242/jcs.108670

    PubMed Central  CAS  PubMed  Google Scholar 

  • Elsum I, Yates L, Humbert PO, Richardson HE (2012) The Scribble-Dlg-Lgl polarity module in development and cancer: from flies to man. Essays Biochem 53:141–168. doi:10.1042/bse0530141, bse0530141 [pii]

    CAS  PubMed  Google Scholar 

  • Elsum IA, Martin C, Humbert PO (2013a) Scribble regulates an EMT-polarity pathway through modulation of MAPK-ERK signaling to mediate junction formation. J Cell Sci. doi:10.1242/jcs.129387, jcs.129387 [pii]

    PubMed  Google Scholar 

  • Elsum IA, Yates LL, Pearson HB, Phesse TJ, Long F, O’Donoghue R, Ernst M, Cullinane C, Humbert PO (2013b) Scrib heterozygosity predisposes to lung cancer and cooperates with KRas hyperactivation to accelerate lung cancer progression in vivo. Oncogene. doi:10.1038/onc.2013.498, onc2013498 [pii]

    PubMed  Google Scholar 

  • Etienne-Manneville S, Manneville JB, Nicholls S, Ferenczi MA, Hall A (2005) Cdc42 and Par6-PKCzeta regulate the spatially localized association of Dlg1 and APC to control cell polarization. J Cell Biol 170(6):895–901

    PubMed Central  CAS  PubMed  Google Scholar 

  • Facciuto F, Cavatorta AL, Valdano MB, Marziali F, Gardiol D (2012) Differential expression of PDZ domain-containing proteins in human diseases - challenging topics and novel issues. FEBS J 279(19):3538–3548. doi:10.1111/j.1742-4658.2012.08699.x

    CAS  PubMed  Google Scholar 

  • Feigin ME, Akshinthala SD, Araki K, Rosenberg AZ, Muthuswamy LB, Martin B, Lehmann BD, Berman HK, Pietenpol JA, Cardiff RD, Muthuswamy SK (2014) Mislocalization of the cell polarity protein scribble promotes mammary tumorigenesis and is associated with basal breast cancer. Cancer Res 74(11):3180–3194. doi:10.1158/0008-5472.CAN-13-3415, 0008-5472.CAN-13-3415 [pii]

    CAS  PubMed  Google Scholar 

  • Feng W, Wu H, Chan LN, Zhang M (2008) Par-3-mediated junctional localization of the lipid phosphatase PTEN is required for cell polarity establishment. J Biol Chem 283(34):23440–23449. doi:10.1074/jbc.M802482200, M802482200 [pii]

    CAS  PubMed  Google Scholar 

  • Fernandez-Medarde A, Santos E (2011) Ras in cancer and developmental diseases. Genes Cancer 2(3):344–358. doi:10.1177/1947601911411084, 10.1177_1947601911411084 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fichelson P, Jagut M, Lepanse S, Lepesant JA, Huynh JR (2010) Lethal giant larvae is required with the par genes for the early polarization of the Drosophila oocyte. Development 137(5):815–824. doi:10.1242/dev.045013

    CAS  PubMed  Google Scholar 

  • Firestein BL, Rongo C (2001) DLG-1 is a MAGUK similar to SAP97 and is required for adherens junction formation. Mol Biol Cell 12(11):3465–3475

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fortini ME (2009) Notch signaling: the core pathway and its posttranslational regulation. Dev Cell 16(5):633–647. doi:10.1016/j.devcel.2009.03.010, S1534-5807(09)00131-2 [pii]

    CAS  PubMed  Google Scholar 

  • Frese KK, Latorre IJ, Chung SH, Caruana G, Bernstein A, Jones SN, Donehower LA, Justice MJ, Garner CC, Javier RT (2006) Oncogenic function for the Dlg1 mammalian homolog of the Drosophila discs-large tumor suppressor. EMBO J 25(6):1406–1417

    PubMed Central  CAS  PubMed  Google Scholar 

  • Froldi F, Ziosi M, Garoia F, Pession A, Grzeschik NA, Bellosta P, Strand D, Richardson HE, Grifoni D (2010) The lethal giant larvae tumour suppressor mutation requires dMyc oncoprotein to promote clonal malignancy. BMC Biol 8:33

    PubMed Central  PubMed  Google Scholar 

  • Funke L, Dakoji S, Bredt DS (2005) Membrane-associated guanylate kinases regulate adhesion and plasticity at cell junctions. Annu Rev Biochem 74:219–245

    CAS  PubMed  Google Scholar 

  • Gangar A, Rossi G, Andreeva A, Hales R, Brennwald P (2005) Structurally conserved interaction of Lgl family with SNAREs is critical to their cellular function. Curr Biol 15(12):1136–1142

    CAS  PubMed  Google Scholar 

  • Garcia RA, Vasudevan K, Buonanno A (2000) The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses. Proc Natl Acad Sci U S A 97(7):3596–3601. doi:10.1073/pnas.070042497, 070042497 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gardiol D, Kuhne C, Glaunsinger B, Lee SS, Javier R, Banks L (1999) Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation. Oncogene 18(40):5487–5496

    CAS  PubMed  Google Scholar 

  • Gardoni F, Marcello E, Di Luca M (2009) Postsynaptic density-membrane associated guanylate kinase proteins (PSD-MAGUKs) and their role in CNS disorders. Neuroscience 158(1):324–333. doi:10.1016/j.neuroscience.2008.07.068, S0306-4522(08)01130-5 [pii]

    CAS  PubMed  Google Scholar 

  • Gateff E, Schneiderman HA (1974) Developmental capacities of benign and malignant neoplasms of Drosophila. Roux’s Arch Dev Biol 176:23–65

    Google Scholar 

  • Gaudet S, Langlois MJ, Lue RA, Rivard N, Viel A (2011) The MEK2-binding tumor suppressor hDlg is recruited by E-cadherin to the midbody ring. BMC Cell Biol 12:55. doi:10.1186/1471-2121-12-55, 1471-2121-12-55 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gladstone M, Su TT (2011) Chemical genetics and drug screening in Drosophila cancer models. J Genet Genomics 38(10):497–504. doi:10.1016/j.jgg.2011.09.003

    CAS  PubMed  Google Scholar 

  • Gmyrek GB, Graham DB, Sandoval GJ, Blaufuss GS, Akilesh HM, Fujikawa K, Xavier RJ, Swat W (2013) Polarity gene discs large homolog 1 regulates the generation of memory T cells. Eur J Immunol 43(5):1185–1194. doi:10.1002/eji.201142362

    PubMed Central  CAS  PubMed  Google Scholar 

  • Godde NJ, Sheridan JM, Smith LK, Pearson HB, Britt KL, Galea RC, Yates LL, Visvader JE, Humbert PO (2014) Scribble modulates the MAPK/Fra1 pathway to disrupt luminal and ductal integrity and suppress tumour formation in the mammary gland. PLoS Genet 10(5):e1004323. doi:10.1371/journal.pgen.1004323, PGENETICS-D-13-03014 [pii]

    PubMed Central  PubMed  Google Scholar 

  • Goh LH, Zhou X, Lee MC, Lin S, Wang H, Luo Y, Yang X (2013) Clueless regulates aPKC activity and promotes self-renewal cell fate in Drosophila lgl mutant larval brains. Dev Biol 381(2):353–364. doi:10.1016/j.ydbio.2013.06.031, S0012-1606(13)00364-3 [pii]

    CAS  PubMed  Google Scholar 

  • Gont A, Hanson JE, Lavictoire SJ, Parolin DA, Daneshmand M, Restall IJ, Soucie M, Nicholas G, Woulfe J, Kassam A, Da Silva VF, Lorimer IA (2013) PTEN loss represses glioblastoma tumor initiating cell differentiation via inactivation of Lgl1. Oncotarget 4(8):1266–1279, doi:1164 [pii]

    PubMed Central  PubMed  Google Scholar 

  • Gonzalez C (2013) Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics. Nat Rev Cancer 13(3):172–183. doi:10.1038/nrc3461

    CAS  PubMed  Google Scholar 

  • Grifoni D, Froldi F, Pession A (2013) Connecting epithelial polarity, proliferation and cancer in Drosophila: the many faces of lgl loss of function. Int J Dev Biol 57(9–10):677–687. doi:10.1387/ijdb.130285dg

    CAS  PubMed  Google Scholar 

  • Grosshans BL, Andreeva A, Gangar A, Niessen S, Yates JR 3rd, Brennwald P, Novick P (2006) The yeast lgl family member Sro7p is an effector of the secretory Rab GTPase Sec4p. J Cell Biol 172(1):55–66

    PubMed Central  CAS  PubMed  Google Scholar 

  • Grusche FA, Degoutin JL, Richardson HE, Harvey KF (2011) The Salvador/Warts/Hippo pathway controls regenerative tissue growth in Drosophila melanogaster. Dev Biol 350(2):255–266

    CAS  PubMed  Google Scholar 

  • Grzeschik NA, Parsons LM, Allott ML, Harvey KF, Richardson HE (2010a) Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Curr Biol 20(7):573–581. doi:10.1016/j.cub.2010.01.055, S0960-9822(10)00151-X [pii]

    CAS  PubMed  Google Scholar 

  • Grzeschik NA, Parsons LM, Richardson HE (2010b) Lgl, the SWH pathway and tumorigenesis: it’s a matter of context & competition! Cell Cycle 9(16):3202–3212. doi:10.4161/cc.9.16.12633, 12633 [pii]

    CAS  PubMed  Google Scholar 

  • Haenfler JM, Kuang C, Lee CY (2012) Cortical aPKC kinase activity distinguishes neural stem cells from progenitor cells by ensuring asymmetric segregation of Numb. Dev Biol 365(1):219–228. doi:10.1016/j.ydbio.2012.02.027, S0012-1606(12)00104-2 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Halaoui R, McCaffrey L (2014) Rewiring cell polarity signaling in cancer. Oncogene. doi:10.1038/onc.2014.59

    PubMed  Google Scholar 

  • Hattendorf DA, Andreeva A, Gangar A, Brennwald PJ, Weis WI (2007) Structure of the yeast polarity protein Sro7 reveals a SNARE regulatory mechanism. Nature 446(7135):567–571. doi:10.1038/nature05635, nature05635 [pii]

    CAS  PubMed  Google Scholar 

  • Hava D, Forster U, Matsuda M, Cui S, Link BA, Eichhorst J, Wiesner B, Chitnis A, Abdelilah-Seyfried S (2009) Apical membrane maturation and cellular rosette formation during morphogenesis of the zebrafish lateral line. J Cell Sci 122(Pt 5):687–695. doi:10.1242/jcs.032102

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hawkins ED, Oliaro J, Kallies A, Belz GT, Filby A, Hogan T, Haynes N, Ramsbottom KM, Van Ham V, Kinwell T, Seddon B, Davies D, Tarlinton D, Lew AM, Humbert PO, Russell SM (2013) Regulation of asymmetric cell division and polarity by Scribble is not required for humoral immunity. Nat Commun 4:1801. doi:10.1038/ncomms2796

    PubMed  Google Scholar 

  • Hawkins ED, Oliaro J, Ramsbottom KM, Ting SB, Sacirbegovic F, Harvey M, Kinwell T, Ghysdael J, Johnstone RW, Humbert PO, Russell SM (2014) Lethal giant larvae 1 tumour suppressor activity is not conserved in models of Mammalian T and B cell leukaemia. PLoS One 9(1):e87376. doi:10.1371/journal.pone.0087376

    PubMed Central  PubMed  Google Scholar 

  • Heidel FH, Bullinger L, Arreba-Tutusaus P, Wang Z, Gaebel J, Hirt C, Niederwieser D, Lane SW, Dohner K, Vasioukhin V, Fischer T, Armstrong SA (2013) The cell fate determinant Llgl1 influences HSC fitness and prognosis in AML. J Exp Med 210(1):15–22. doi:10.1084/jem.20120596, jem.20120596 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hendrickx A, Beullens M, Ceulemans H, Den Abt T, Van Eynde A, Nicolaescu E, Lesage B, Bollen M (2009) Docking motif-guided mapping of the interactome of protein phosphatase-1. Chem Biol 16(4):365–371. doi:10.1016/j.chembiol.2009.02.012, S1074-5521(09)00079-9 [pii]

    CAS  PubMed  Google Scholar 

  • Hering H, Sheng M (2002) Direct interaction of Frizzled-1, -2, -4, and -7 with PDZ domains of PSD-95. FEBS Lett 521(1–3):185–189

    CAS  PubMed  Google Scholar 

  • Hoege C, Constantinescu AT, Schwager A, Goehring NW, Kumar P, Hyman AA (2010) LGL can partition the cortex of one-cell Caenorhabditis elegans embryos into two domains. Curr Biol 20(14):1296–1303. doi:10.1016/j.cub.2010.05.061, S0960-9822(10)00710-4 [pii]

    CAS  PubMed  Google Scholar 

  • Hogan C (2012) Impact of interactions between normal and transformed epithelial cells and the relevance to cancer. Cell Mol Life Sci 69(2):203–213. doi:10.1007/s00018-011-0806-3

    CAS  PubMed  Google Scholar 

  • Huganir RL, Nicoll RA (2013) AMPARs and synaptic plasticity: the last 25 years. Neuron 80(3):704–717. doi:10.1016/j.neuron.2013.10.025

    PubMed Central  CAS  PubMed  Google Scholar 

  • Humbert P, Russell S, Richardson H (2003) Dlg, Scribble and Lgl in cell polarity, cell proliferation and cancer. Bioessays 25(6):542–553

    CAS  PubMed  Google Scholar 

  • Humbert PO, Dow LE, Russell SM (2006) The Scribble and Par complexes in polarity and migration: friends or foes? Trends Cell Biol 16(12):622–630. doi:10.1016/j.tcb.2006.10.005

    CAS  PubMed  Google Scholar 

  • Humbert PO, Grzeschik NA, Brumby AM, Galea R, Elsum I, Richardson HE (2008) Control of tumourigenesis by the Scribble/Dlg/Lgl polarity module. Oncogene 27(55):6888–6907. doi:10.1038/onc.2008.341, onc2008341 [pii]

    CAS  PubMed  Google Scholar 

  • Humphries LA, Shaffer MH, Sacirbegovic F, Tomassian T, McMahon KA, Humbert PO, Silva O, Round JL, Takamiya K, Huganir RL, Burkhardt JK, Russell SM, Miceli MC (2012) Characterization of in vivo Dlg1 deletion on T cell development and function. PLoS One 7(9):e45276. doi:10.1371/journal.pone.0045276

    PubMed Central  CAS  PubMed  Google Scholar 

  • Igaki T, Pagliarini RA, Xu T (2006) Loss of cell polarity drives tumor growth and invasion through JNK activation in Drosophila. Curr Biol 16(11):1139–1146. doi:10.1016/j.cub.2006.04.042, S0960-9822(06)01539-9 [pii]

    CAS  PubMed  Google Scholar 

  • Igaki T, Pastor-Pareja JC, Aonuma H, Miura M, Xu T (2009) Intrinsic tumor suppression and epithelial maintenance by endocytic activation of Eiger/TNF signaling in Drosophila. Dev Cell 16(3):458–465. doi:10.1016/j.devcel.2009.01.002, S1534-5807(09)00030-6 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Iizuka-Kogo A, Ishidao T, Akiyama T, Senda T (2007) Abnormal development of urogenital organs in Dlgh1-deficient mice. Development 134(9):1799–1807

    CAS  PubMed  Google Scholar 

  • Ishidate T, Matsumine A, Toyoshima K, Akiyama T (2000) The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase. Oncogene 19(3):365–372

    CAS  PubMed  Google Scholar 

  • Ivarsson Y, Arnold R, McLaughlin M, Nim S, Joshi R, Ray D, Liu B, Teyra J, Pawson T, Moffat J, Li SS, Sidhu SS, Kim PM (2014) Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes. Proc Natl Acad Sci U S A 111(7):2542–2547. doi:10.1073/pnas.1312296111

    PubMed Central  CAS  PubMed  Google Scholar 

  • Javier RT, Rice AP (2011) Emerging theme: cellular PDZ proteins as common targets of pathogenic viruses. J Virol 85(22):11544–11556. doi:10.1128/JVI.05410-11

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jiang Y, Scott KL, Kwak SJ, Chen R, Mardon G (2011) Sds22/PP1 links epithelial integrity and tumor suppression via regulation of myosin II and JNK signaling. Oncogene 30(29):3248–3260. doi:10.1038/onc.2011.46, onc201146 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Justice N, Roegiers F, Jan LY, Jan YN (2003) Lethal giant larvae acts together with numb in notch inhibition and cell fate specification in the Drosophila adult sensory organ precursor lineage. Curr Biol 13(9):778–783, doi:S0960982203002884 [pii]

    CAS  PubMed  Google Scholar 

  • Kallay LM, McNickle A, Brennwald PJ, Hubbard AL, Braiterman LT (2006) Scribble associates with two polarity proteins, Lgl2 and Vangl2, via distinct molecular domains. J Cell Biochem 99(2):647–664

    CAS  PubMed  Google Scholar 

  • Kaplan NA, Tolwinski NS (2010) Spatially defined Dsh-Lgl interaction contributes to directional tissue morphogenesis. J Cell Sci 123(Pt 18):3157–3165

    CAS  PubMed  Google Scholar 

  • Katoh M, Katoh M (2004) Identification and characterization of human GUKH2 gene in silico. Int J Oncol 24(4):1033–1038

    CAS  PubMed  Google Scholar 

  • Kemphues KJ, Priess JR, Morton DG, Cheng NS (1988) Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell 52(3):311–320, doi:S0092-8674(88)80024-2 [pii]

    CAS  PubMed  Google Scholar 

  • King CG, Koehli S, Hausmann B, Schmaler M, Zehn D, Palmer E (2012) T cell affinity regulates asymmetric division, effector cell differentiation, and tissue pathology. Immunity 37(4):709–720. doi:10.1016/j.immuni.2012.06.021

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kiyono T, Hiraiwa A, Fujita M, Hayashi Y, Akiyama T, Ishibashi M (1997) Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci U S A 94(21):11612–11616

    PubMed Central  CAS  PubMed  Google Scholar 

  • Klezovitch O, Fernandez TE, Tapscott SJ, Vasioukhin V (2004) Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice. Genes Dev 18(5):559–571

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kobe B, Kajava AV (2001) The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol 11(6):725–732

    CAS  PubMed  Google Scholar 

  • Koh YH, Popova E, Thomas U, Griffith LC, Budnik V (1999) Regulation of DLG localization at synapses by CaMKII-dependent phosphorylation. Cell 98(3):353–363

    CAS  PubMed  Google Scholar 

  • Kong K, Kumar M, Taruishi M, Javier RT (2014) The human adenovirus E4-ORF1 protein subverts discs large 1 to mediate membrane recruitment and dysregulation of phosphatidylinositol 3-kinase. PLoS Pathog 10(5):e1004102. doi:10.1371/journal.ppat.1004102

    PubMed Central  PubMed  Google Scholar 

  • Koppen M, Simske JS, Sims PA, Firestein BL, Hall DH, Radice AD, Rongo C, Hardin JD (2001) Cooperative regulation of AJM-1 controls junctional integrity in Caenorhabditis elegans epithelia. Nat Cell Biol 3(11):983–991

    CAS  PubMed  Google Scholar 

  • Kronen MR, Schoenfelder KP, Klein AM, Nystul TG (2014) Basolateral junction proteins regulate competition for the follicle stem cell niche in the Drosophila ovary. PLoS One 9(7):e101085. doi:10.1371/journal.pone.0101085, PONE-D-14-21899 [pii]

    PubMed Central  PubMed  Google Scholar 

  • Kulshammer E, Uhlirova M (2013) The actin cross-linker Filamin/Cheerio mediates tumor malignancy downstream of JNK signaling. J Cell Sci 126(Pt 4):927–938. doi:10.1242/jcs.114462, jcs.114462 [pii]

    PubMed  Google Scholar 

  • Kuwada SK, Lund KA, Li XF, Cliften P, Amsler K, Opresko LK, Wiley HS (1998) Differential signaling and regulation of apical vs. basolateral EGFR in polarized epithelial cells. Am J Physiol 275(6 Pt 1):C1419–C1428

    CAS  PubMed  Google Scholar 

  • Lahuna O, Quellari M, Achard C, Nola S, Meduri G, Navarro C, Vitale N, Borg JP, Misrahi M (2005) Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 pathway. EMBO J 24(7):1364–1374

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lambert JM, Lambert QT, Reuther GW, Malliri A, Siderovski DP, Sondek J, Collard JG, Der CJ (2002) Tiam1 mediates Ras activation of Rac by a PI(3)K-independent mechanism. Nat Cell Biol 4(8):621–625. doi:10.1038/ncb833, ncb833 [pii]

    CAS  PubMed  Google Scholar 

  • Langevin J, Le Borgne R, Rosenfeld F, Gho M, Schweisguth F, Bellaiche Y (2005) Lethal giant larvae controls the localization of notch-signaling regulators numb, neuralized, and Sanpodo in Drosophila sensory-organ precursor cells. Curr Biol 15(10):955–962. doi:10.1016/j.cub.2005.04.054, S0960-9822(05)00455-0 [pii]

    CAS  PubMed  Google Scholar 

  • Lasserre R, Charrin S, Cuche C, Danckaert A, Thoulouze MI, de Chaumont F, Duong T, Perrault N, Varin-Blank N, Olivo-Marin JC, Etienne-Manneville S, Arpin M, Di Bartolo V, Alcover A (2010) Ezrin tunes T-cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse. EMBO J 29(14):2301–2314. doi:10.1038/emboj.2010.127, emboj2010127 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lee SS, Weiss RS, Javier RT (1997) Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci U S A 94(13):6670–6675

    PubMed Central  CAS  PubMed  Google Scholar 

  • Legouis R, Gansmuller A, Sookhareea S, Bosher JM, Baillie DL, Labouesse M (2000) LET-413 is a basolateral protein required for the assembly of adherens junctions in Caenorhabditis elegans. Nat Cell Biol 2(7):415–422

    CAS  PubMed  Google Scholar 

  • Legouis R, Jaulin-Bastard F, Schott S, Navarro C, Borg JP, Labouesse M (2003) Basolateral targeting by leucine-rich repeat domains in epithelial cells. EMBO Rep 4(11):1096–1102

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lei Y, Zhu H, Duhon C, Yang W, Ross ME, Shaw GM, Finnell RH (2013) Mutations in planar cell polarity gene SCRIB are associated with spina bifida. PLoS One 8(7):e69262. doi:10.1371/journal.pone.0069262

    PubMed Central  CAS  PubMed  Google Scholar 

  • Leong GR, Goulding KR, Amin N, Richardson HE, Brumby AM (2009) Scribble mutants promote aPKC and JNK-dependent epithelial neoplasia independently of Crumbs. BMC Biol 7:62

    PubMed Central  PubMed  Google Scholar 

  • Li Q, Feng S, Yu L, Zhao G, Li M (2011a) Requirements of Lgl in cell differentiation and motility during Drosophila ovarian follicular epithelium morphogenesis. Fly (Austin) 5(2):81–87

    Google Scholar 

  • Li X, Yang H, Liu J, Schmidt MD, Gao T (2011b) Scribble-mediated membrane targeting of PHLPP1 is required for its negative regulation of Akt. EMBO Rep. doi:10.1038/embor.2011.106, embor2011106 [pii]

    Google Scholar 

  • Liu W, Chen E, Zhao XW, Wan ZP, Gao YR, Davey A, Huang E, Zhang L, Crocetti J, Sandoval G, Joyce MG, Miceli C, Lukszo J, Aravind L, Swat W, Brzostowski J, Pierce SK (2012) The scaffolding protein synapse-associated protein 97 is required for enhanced signaling through isotype-switched IgG memory B cell receptors. Sci Signal 5(235):ra54. doi:10.1126/scisignal.2002820

    PubMed Central  PubMed  Google Scholar 

  • Lohia M, Qin Y, Macara IG (2012) The Scribble polarity protein stabilizes E-cadherin/p120-catenin binding and blocks retrieval of E-cadherin to the Golgi. PLoS One 7(11):e51130. doi:10.1371/journal.pone.0051130, PONE-D-12-27172 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lolo FN, Casas-Tinto S, Moreno E (2012) Cell competition time line: winners kill losers, which are extruded and engulfed by hemocytes. Cell Rep 2(3):526–539. doi:10.1016/j.celrep.2012.08.012, S2211-1247(12)00237-9 [pii]

    CAS  PubMed  Google Scholar 

  • Ludford-Menting MJ, Oliaro J, Sacirbegovic F, Cheah ET, Pedersen N, Thomas SJ, Pasam A, Iazzolino R, Dow LE, Waterhouse NJ, Murphy A, Ellis S, Smyth MJ, Kershaw MH, Darcy PK, Humbert PO, Russell SM (2005) A network of PDZ-containing proteins regulates T cell polarity and morphology during migration and immunological synapse formation. Immunity 22(6):737–748. doi:10.1016/j.immuni.2005.04.009

    CAS  PubMed  Google Scholar 

  • Luyten A, Mortier E, Van Campenhout C, Taelman V, Degeest G, Wuytens G, Lambaerts K, David G, Bellefroid EJ, Zimmermann P (2008) The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling. Mol Biol Cell 19(4):1594–1604. doi:10.1091/mbc.E07-08-0832, E07-08-0832 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Macara IG, Mili S (2008) Polarity and differential inheritance–universal attributes of life? Cell 135(5):801–812. doi:10.1016/j.cell.2008.11.006, S0092-8674(08)01392-5 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mahoney ZX, Sammut B, Xavier RJ, Cunningham J, Go G, Brim KL, Stappenbeck TS, Miner JH, Swat W (2006) Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter. Proc Natl Acad Sci U S A 103(52):19872–19877

    PubMed Central  CAS  PubMed  Google Scholar 

  • Maiga O, Philippe M, Kotelevets L, Chastre E, Benadda S, Pidard D, Vranckx R, Walch L (2011) Identification of mitogen-activated protein/extracellular signal-responsive kinase kinase 2 as a novel partner of the scaffolding protein human homolog of disc-large. FEBS J 278(15):2655–2665. doi:10.1111/j.1742-4658.2011.08192.x

    CAS  PubMed  Google Scholar 

  • Manneville JB, Jehanno M, Etienne-Manneville S (2010) Dlg1 binds GKAP to control dynein association with microtubules, centrosome positioning, and cell polarity. J Cell Biol 191(3):585–598. doi:10.1083/jcb.201002151, jcb.201002151 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Massimi P, Narayan N, Cuenda A, Banks L (2006) Phosphorylation of the discs large tumour suppressor protein controls its membrane localisation and enhances its susceptibility to HPV E6-induced degradation. Oncogene 25(31):4276–4285

    CAS  PubMed  Google Scholar 

  • Massimi P, Narayan N, Thomas M, Gammoh N, Strand S, Strand D, Banks L (2008) Regulation of the hDlg/hScrib/Hugl-1 tumour suppressor complex. Exp Cell Res 314(18):3306–3317

    CAS  PubMed  Google Scholar 

  • Mathew D, Gramates LS, Packard M, Thomas U, Bilder D, Perrimon N, Gorczyca M, Budnik V (2002) Recruitment of scribble to the synaptic scaffolding complex requires GUK-holder, a novel DLG binding protein. Curr Biol 12(7):531–539

    CAS  PubMed  Google Scholar 

  • Matsumine A, Ogai A, Senda T, Okumura N, Satoh K, Baeg GH, Kawahara T, Kobayashi S, Okada M, Toyoshima K, Akiyama T (1996) Binding of APC to the human homolog of the Drosophila discs large tumor suppressor protein. Science 272(5264):1020–1023

    CAS  PubMed  Google Scholar 

  • Mayer BJ (2001) SH3 domains: complexity in moderation. J Cell Sci 114(Pt 7):1253–1263

    CAS  PubMed  Google Scholar 

  • McGee AW, Topinka JR, Hashimoto K, Petralia RS, Kakizawa S, Kauer F, Aguilera-Moreno A, Wenthold RJ, Kano M, Bredt DS (2001) PSD-93 knock-out mice reveal that neuronal MAGUKs are not required for development or function of parallel fiber synapses in cerebellum. J Neurosci 21(9):3085–3091

    CAS  PubMed  Google Scholar 

  • McMahon L, Legouis R, Vonesch JL, Labouesse M (2001) Assembly of C. elegans apical junctions involves positioning and compaction by LET-413 and protein aggregation by the MAGUK protein DLG-1. J Cell Sci 114(Pt 12):2265–2277

    CAS  PubMed  Google Scholar 

  • Mechler BM, McGinnis W, Gehring WJ (1985) Molecular cloning of lethal(2)giant larvae, a recessive oncogene of Drosophila melanogaster. EMBO J 4(6):1551–1557

    PubMed Central  CAS  PubMed  Google Scholar 

  • Menendez J, Perez-Garijo A, Calleja M, Morata G (2010) A tumor-suppressing mechanism in Drosophila involving cell competition and the Hippo pathway. Proc Natl Acad Sci U S A 107(33):14651–14656

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mertens AE, Rygiel TP, Olivo C, van der Kammen R, Collard JG (2005) The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex. J Cell Biol 170(7):1029–1037. doi:10.1083/jcb.200502129, jcb.200502129 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Metodieva G, Nogueira-de-Souza NC, Greenwood C, Al-Janabi K, Leng L, Bucala R, Metodiev MV (2013) CD74-dependent deregulation of the tumor suppressor scribble in human epithelial and breast cancer cells. Neoplasia 15(6):660–668

    PubMed Central  CAS  PubMed  Google Scholar 

  • Meyer MP, Trimmer JS, Gilthorpe JD, Smith SJ (2005) Characterization of zebrafish PSD-95 gene family members. J Neurobiol 63(2):91–105. doi:10.1002/neu.20118

    CAS  PubMed  Google Scholar 

  • Michaelis UR, Chavakis E, Kruse C, Jungblut B, Kaluza D, Wandzioch K, Manavski Y, Heide H, Santoni MJ, Potente M, Eble JA, Borg JP, Brandes RP (2013) The polarity protein Scrib is essential for directed endothelial cell migration. Circ Res 112(6):924–934. doi:10.1161/CIRCRESAHA.112.300592

    CAS  PubMed  Google Scholar 

  • Migaud M, Charlesworth P, Dempster M, Webster LC, Watabe AM, Makhinson M, He Y, Ramsay MF, Morris RG, Morrison JH, O’Dell TJ, Grant SG (1998) Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature 396(6710):433–439

    CAS  PubMed  Google Scholar 

  • Montcouquiol M, Rachel RA, Lanford PJ, Copeland NG, Jenkins NA, Kelley MW (2003) Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. Nature 423(6936):173–177. doi:10.1038/nature01618, nature01618 [pii]

    CAS  PubMed  Google Scholar 

  • Moreau MM, Piguel N, Papouin T, Koehl M, Durand CM, Rubio ME, Loll F, Richard EM, Mazzocco C, Racca C, Oliet SH, Abrous DN, Montcouquiol M, Sans N (2010) The planar polarity protein Scribble1 is essential for neuronal plasticity and brain function. J Neurosci 30(29):9738–9752. doi:10.1523/JNEUROSCI.6007-09.2010

    CAS  PubMed  Google Scholar 

  • Morin X, Bellaiche Y (2011) Mitotic spindle orientation in asymmetric and symmetric cell divisions during animal development. Dev Cell 21(1):102–119. doi:10.1016/j.devcel.2011.06.012, S1534-5807(11)00246-2 [pii]

    CAS  PubMed  Google Scholar 

  • Murdoch JN, Henderson DJ, Doudney K, Gaston-Massuet C, Phillips HM, Paternotte C, Arkell R, Stanier P, Copp AJ (2003) Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse. Hum Mol Genet 12(2):87–98

    CAS  PubMed  Google Scholar 

  • Musch A, Cohen D, Yeaman C, Nelson WJ, Rodriguez-Boulan E, Brennwald PJ (2002) Mammalian homolog of Drosophila tumor suppressor lethal (2) giant larvae interacts with basolateral exocytic machinery in Madin-Darby canine kidney cells. Mol Biol Cell 13(1):158–168

    CAS  PubMed  Google Scholar 

  • Nagasaka K, Massimi P, Pim D, Subbaiah VK, Kranjec C, Nakagawa S, Yano T, Taketani Y, Banks L (2010a) The mechanism and implications of hScrib regulation of ERK. Small GTPases 1(2):108–112. doi:10.4161/sgtp.1.2.13649, 2154-1248-1-2-6 [pii]

    PubMed Central  PubMed  Google Scholar 

  • Nagasaka K, Pim D, Massimi P, Thomas M, Tomaic V, Subbaiah VK, Kranjec C, Nakagawa S, Yano T, Taketani Y, Myers M, Banks L (2010b) The cell polarity regulator hScrib controls ERK activation through a KIM site-dependent interaction. Oncogene 29(38):5311–5321. doi:10.1038/onc.2010.265, onc2010265 [pii]

    CAS  PubMed  Google Scholar 

  • Nagasaka K, Seiki T, Yamashita A, Massimi P, Subbaiah VK, Thomas M, Kranjec C, Kawana K, Nakagawa S, Yano T, Taketani Y, Fujii T, Kozuma S, Banks L (2013) A novel interaction between hScrib and PP1gamma downregulates ERK signaling and suppresses oncogene-induced cell transformation. PLoS One 8(1):e53752. doi:10.1371/journal.pone.0053752, PONE-D-12-02664 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Naim E, Bernstein A, Bertram JF, Caruana G (2005) Mutagenesis of the epithelial polarity gene, discs large 1, perturbs nephrogenesis in the developing mouse kidney. Kidney Int 68(3):955–965. doi:10.1111/j.1523-1755.2005.00489.x, KID489 [pii]

    CAS  PubMed  Google Scholar 

  • Nakagawa S, Huibregtse JM (2000) Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase. Mol Cell Biol 20(21):8244–8253

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nakajima YI, Meyer EJ, Kroesen A, McKinney SA, Gibson MC (2013) Epithelial junctions maintain tissue architecture by directing planar spindle orientation. Nature. doi:10.1038/nature12335

    PubMed Central  Google Scholar 

  • Narayan N, Subbaiah VK, Banks L (2009) The high-risk HPV E6 oncoprotein preferentially targets phosphorylated nuclear forms of hDlg. Virology 387(1):1–4. doi:10.1016/j.virol.2009.02.030

    CAS  PubMed  Google Scholar 

  • Narayanan AS, Reyes SB, Um K, McCarty JH, Tolias KF (2013) The Rac-GAP Bcr is a novel regulator of the PAR complex that controls cell polarity. Mol Biol Cell 24(24):3857–3868. doi:10.1091/mbc.E13-06-0333, mbc.E13-06-0333 [pii]

    PubMed Central  PubMed  Google Scholar 

  • Navarro C, Nola S, Audebert S, Santoni MJ, Arsanto JP, Ginestier C, Marchetto S, Jacquemier J, Isnardon D, Le Bivic A, Birnbaum D, Borg JP (2005) Junctional recruitment of mammalian Scribble relies on E-cadherin engagement. Oncogene 24(27):4330–4339

    CAS  PubMed  Google Scholar 

  • Nelson WJ (2003) Adaptation of core mechanisms to generate cell polarity. Nature 422(6933):766–774. doi:10.1038/nature01602, nature01602 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nithianantharajah J, Komiyama NH, McKechanie A, Johnstone M, Blackwood DH, St Clair D, Emes RD, van de Lagemaat LN, Saksida LM, Bussey TJ, Grant SG (2013) Synaptic scaffold evolution generated components of vertebrate cognitive complexity. Nat Neurosci 16(1):16–24. doi:10.1038/nn.3276

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nola S, Sebbagh M, Marchetto S, Osmani N, Nourry C, Audebert S, Navarro C, Rachel R, Montcouquiol M, Sans N, Etienne-Manneville S, Borg JP, Santoni MJ (2008) Scrib regulates PAK activity during the cell migration process. Hum Mol Genet 17(22):3552–3565. doi:10.1093/hmg/ddn248, ddn248 [pii]

    CAS  PubMed  Google Scholar 

  • Nolan ME, Aranda V, Lee S, Lakshmi B, Basu S, Allred DC, Muthuswamy SK (2008) The polarity protein Par6 induces cell proliferation and is overexpressed in breast cancer. Cancer Res 68(20):8201–8209. doi:10.1158/0008-5472.CAN-07-6567, 68/20/8201 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Norman M, Wisniewska KA, Lawrenson K, Garcia-Miranda P, Tada M, Kajita M, Mano H, Ishikawa S, Ikegawa M, Shimada T, Fujita Y (2012) Loss of Scribble causes cell competition in mammalian cells. J Cell Sci 125(Pt 1):59–66. doi:10.1242/jcs.085803, jcs.085803 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nourry C, Grant SG, Borg JP (2003) PDZ domain proteins: plug and play! Sci STKE 2003(179):RE7

    PubMed  Google Scholar 

  • Ohsawa S, Sugimura K, Takino K, Xu T, Miyawaki A, Igaki T (2011) Elimination of oncogenic neighbors by JNK-mediated engulfment in Drosophila. Dev Cell 20(3):315–328. doi:10.1016/j.devcel.2011.02.007, S1534-5807(11)00076-1 [pii]

    CAS  PubMed  Google Scholar 

  • Ohshiro T, Yagami T, Zhang C, Matsuzaki F (2000) Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast. Nature 408(6812):593–596

    CAS  PubMed  Google Scholar 

  • Okajima M, Takahashi M, Higuchi M, Ohsawa T, Yoshida S, Yoshida Y, Oie M, Tanaka Y, Gejyo F, Fujii M (2008) Human T-cell leukemia virus type 1 Tax induces an aberrant clustering of the tumor suppressor Scribble through the PDZ domain-binding motif dependent and independent interaction. Virus Genes 37(2):231–240. doi:10.1007/s11262-008-0259-4

    CAS  PubMed  Google Scholar 

  • Oliaro J, Van Ham V, Sacirbegovic F, Pasam A, Bomzon Z, Pham K, Ludford-Menting MJ, Waterhouse NJ, Bots M, Hawkins ED, Watt SV, Cluse LA, Clarke CJ, Izon DJ, Chang JT, Thompson N, Gu M, Johnstone RW, Smyth MJ, Humbert PO, Reiner SL, Russell SM (2010) Asymmetric cell division of T cells upon antigen presentation uses multiple conserved mechanisms. J Immunol 185(1):367–375. doi:10.4049/jimmunol.0903627

    PubMed Central  CAS  PubMed  Google Scholar 

  • Osmani N, Vitale N, Borg JP, Etienne-Manneville S (2006) Scrib controls Cdc42 localization and activity to promote cell polarization during astrocyte migration. Curr Biol 16(24):2395–2405. doi:10.1016/j.cub.2006.10.026

    CAS  PubMed  Google Scholar 

  • Pagliarini RA, Xu T (2003) A genetic screen in Drosophila for metastatic behavior. Science 302(5648):1227–1231

    CAS  PubMed  Google Scholar 

  • Pangon L, Van Kralingen C, Abas M, Daly RJ, Musgrove EA, Kohonen-Corish MR (2012) The PDZ-binding motif of MCC is phosphorylated at position -1 and controls lamellipodia formation in colon epithelial cells. Biochim Biophys Acta 1823(6):1058–1067. doi:10.1016/j.bbamcr.2012.03.011, S0167-4889(12)00077-8 [pii]

    CAS  PubMed  Google Scholar 

  • Parsons L, Portela M, Grzeschik N, Richardson HE (2014a) Lgl regulates Notch signaling via endocytosis, independently of aPKC, in the Drosophila developing eye epithelia. Curr Biol 24(18):2073–2084

    CAS  PubMed  Google Scholar 

  • Parsons LM, Grzeschik NA, Richardson HE (2014b) lgl Regulates the Hippo Pathway Independently of Fat/Dachs, Kibra/Expanded/Merlin and dRASSF/dSTRIPAK. Cancers (Basel) 6(2):879–896. doi:10.3390/cancers6020879, cancers6020879 [pii]

    Google Scholar 

  • Pearson HB, Perez-Mancera PA, Dow LE, Ryan A, Tennstedt P, Bogani D, Elsum I, Greenfield A, Tuveson DA, Simon R, Humbert PO (2011) SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia. J Clin Invest 121(11):4257–4267. doi:10.1172/JCI58509, 58509 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pece S, Chiariello M, Murga C, Gutkind JS (1999) Activation of the protein kinase Akt/PKB by the formation of E-cadherin-mediated cell-cell junctions. Evidence for the association of phosphatidylinositol 3-kinase with the E-cadherin adhesion complex. J Biol Chem 274(27):19347–19351

    CAS  PubMed  Google Scholar 

  • Pham K, Sacirbegovic F, Russell SM (2014) Polarized cells, polarized views: asymmetric cell division in hematopoietic cells. Front Immunol 5:26. doi:10.3389/fimmu.2014.00026

    PubMed Central  PubMed  Google Scholar 

  • Phillips HM, Rhee HJ, Murdoch JN, Hildreth V, Peat JD, Anderson RH, Copp AJ, Chaudhry B, Henderson DJ (2007) Disruption of planar cell polarity signaling results in congenital heart defects and cardiomyopathy attributable to early cardiomyocyte disorganization. Circ Res 101(2):137–145. doi:10.1161/CIRCRESAHA.106.142406, CIRCRESAHA.106.142406 [pii]

    CAS  PubMed  Google Scholar 

  • Phua DC, Humbert PO, Hunziker W (2009) Vimentin regulates scribble activity by protecting it from proteasomal degradation. Mol Biol Cell 20(12):2841–2855. doi:10.1091/mbc.E08-02-0199

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pim D, Bergant M, Boon SS, Ganti K, Kranjec C, Massimi P, Subbaiah VK, Thomas M, Tomaic V, Banks L (2012) Human papillomaviruses and the specificity of PDZ domain targeting. FEBS J 279(19):3530–3537. doi:10.1111/j.1742-4658.2012.08709.x

    CAS  PubMed  Google Scholar 

  • Pinal N, Goberdhan DC, Collinson L, Fujita Y, Cox IM, Wilson C, Pichaud F (2006) Regulated and polarized PtdIns(3,4,5)P3 accumulation is essential for apical membrane morphogenesis in photoreceptor epithelial cells. Curr Biol 16(2):140–149. doi:10.1016/j.cub.2005.11.068, S0960-9822(05)01518-6 [pii]

    CAS  PubMed  Google Scholar 

  • Qin Y, Capaldo C, Gumbiner BM, Macara IG (2005) The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin. J Cell Biol 171(6):1061–1071. doi:10.1083/jcb.200506094

    PubMed Central  CAS  PubMed  Google Scholar 

  • Reischauer S, Levesque MP, Nusslein-Volhard C, Sonawane M (2009) Lgl2 executes its function as a tumor suppressor by regulating ErbB signaling in the zebrafish epidermis. PLoS Genet 5(11):e1000720

    PubMed Central  PubMed  Google Scholar 

  • Reuver SM, Garner CC (1998) E-cadherin mediated cell adhesion recruits SAP97 into the cortical cytoskeleton. J Cell Sci 111(Pt 8):1071–1080

    CAS  PubMed  Google Scholar 

  • Rivard N (2009) Phosphatidylinositol 3-kinase: a key regulator in adherens junction formation and function. Front Biosci 14:510–522, doi:3259 [pii]

    CAS  Google Scholar 

  • Rivera C, Simonson SJ, Yamben IF, Shatadal S, Nguyen MM, Beurg M, Lambert PF, Griep AE (2013) Requirement for Dlgh-1 in planar cell polarity and skeletogenesis during vertebrate development. PLoS One 8(1):e54410. doi:10.1371/journal.pone.0054410, PONE-D-12-18879 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rivera C, Yamben IF, Shatadal S, Waldof M, Robinson ML, Griep AE (2009) Cell-autonomous requirements for Dlg-1 for lens epithelial cell structure and fiber cell morphogenesis. Dev Dyn 238(9):2292–2308. doi:10.1002/dvdy.22036

    PubMed Central  PubMed  Google Scholar 

  • Roberts S, Delury C, Marsh E (2012) The PDZ protein discs-large (DLG): the 'Jekyll and Hyde' of the epithelial polarity proteins. FEBS J 279(19):3549–3558. doi:10.1111/j.1742-4658.2012.08729.x

    CAS  PubMed  Google Scholar 

  • Robinson A, Escuin S, Doudney K, Vekemans M, Stevenson RE, Greene ND, Copp AJ, Stanier P (2012) Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis. Hum Mutat 33(2):440–447. doi:10.1002/humu.21662

    CAS  PubMed  Google Scholar 

  • Roche JP, Packard MC, Moeckel-Cole S, Budnik V (2002) Regulation of synaptic plasticity and synaptic vesicle dynamics by the PDZ protein Scribble. J Neurosci 22(15):6471–6479, doi:20026646

    CAS  PubMed  Google Scholar 

  • Rodriguez-Boulan E, Macara IG (2014) Organization and execution of the epithelial polarity programme. Nat Rev Mol Cell Biol 15(4):225–242. doi:10.1038/nrm3775

    PubMed Central  CAS  PubMed  Google Scholar 

  • Roegiers F, Jan LY, Jan YN (2005) Regulation of membrane localization of Sanpodo by lethal giant larvae and neuralized in asymmetrically dividing cells of Drosophila sensory organs. Mol Biol Cell 16(8):3480–3487

    PubMed Central  CAS  PubMed  Google Scholar 

  • Round JL, Humphries LA, Tomassian T, Mittelstadt P, Zhang M, Miceli MC (2007) Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors. Nat Immunol 8(2):154–161

    CAS  PubMed  Google Scholar 

  • Round JL, Tomassian T, Zhang M, Patel V, Schoenberger SP, Miceli MC (2005) Dlgh1 coordinates actin polymerization, synaptic T cell receptor and lipid raft aggregation, and effector function in T cells. J Exp Med 201(3):419–430

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ryan TJ, Grant SG (2009) The origin and evolution of synapses. Nat Rev Neurosci 10(10):701–712. doi:10.1038/nrn2717, nrn2717 [pii]

    CAS  PubMed  Google Scholar 

  • Sabatini DM (2006) mTOR and cancer: insights into a complex relationship. Nat Rev Cancer 6(9):729–734. doi:10.1038/nrc1974, nrc1974 [pii]

    CAS  PubMed  Google Scholar 

  • Sampedro MN, Bussineau CM, Cotman CW (1981) Postsynaptic density antigens: preparation and characterization of an antiserum against postsynaptic densities. J Cell Biol 90(3):675–686

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sandoval GJ, Graham DB, Gmyrek GB, Akilesh HM, Fujikawa K, Sammut B, Bhattacharya D, Srivatsan S, Kim A, Shaw AS, Yang-Iott K, Bassing CH, Duncavage E, Xavier RJ, Swat W (2013) Novel mechanism of tumor suppression by polarity gene discs large 1 (DLG1) revealed in a murine model of pediatric B-ALL. Cancer Immunol Res 1(6):426–437. doi:10.1158/2326-6066.CIR-13-0065

    PubMed Central  CAS  PubMed  Google Scholar 

  • Santoni M, Pontarotti P, Birnbaum D, Borg J (2002) The LAP family: a phylogenetic point of view. Trends Genet 18(10):494

    CAS  PubMed  Google Scholar 

  • Savi F, Forno I, Faversani A, Luciani A, Caldiera S, Gatti S, Foa P, Ricca D, Bulfamante G, Vaira V, Bosari S (2014) MiR-296/Scribble axe is deregulated in human breast cancer and miR-296 restoration reduces tumor growth in vivo. Clin Sci. doi:10.1042/CS20130580

    PubMed  Google Scholar 

  • Schroeder MC, Chen CL, Gajewski K, Halder G (2013) A non-cell-autonomous tumor suppressor role for Stat in eliminating oncogenic scribble cells. Oncogene 32(38):4471–4479. doi:10.1038/onc.2012.476, onc2012476 [pii]

    CAS  PubMed  Google Scholar 

  • Shewan A, Eastburn DJ, Mostov K (2011) Phosphoinositides in cell architecture. Cold Spring Harb Perspect Biol 3(8):a004796. doi:10.1101/cshperspect.a004796, cshperspect.a004796 [pii]

    PubMed Central  PubMed  Google Scholar 

  • Sjoqvist M, Antfolk D, Ferraris S, Rraklli V, Haga C, Antila C, Mutvei A, Imanishi SY, Holmberg J, Jin S, Eriksson JE, Lendahl U, Sahlgren C (2014) PKCzeta regulates Notch receptor routing and activity in a Notch signaling-dependent manner. Cell Res 24(4):433–450. doi:10.1038/cr.2014.34, cr201434 [pii]

    CAS  PubMed  Google Scholar 

  • Skouloudaki K, Puetz M, Simons M, Courbard JR, Boehlke C, Hartleben B, Engel C, Moeller MJ, Englert C, Bollig F, Schafer T, Ramachandran H, Mlodzik M, Huber TB, Kuehn EW, Kim E, Kramer-Zucker A, Walz G (2009) Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development. Proc Natl Acad Sci U S A 106(21):8579–8584

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sonawane M, Carpio Y, Geisler R, Schwarz H, Maischein HM, Nuesslein-Volhard C (2005) Zebrafish penner/lethal giant larvae 2 functions in hemidesmosome formation, maintenance of cellular morphology and growth regulation in the developing basal epidermis. Development 132(14):3255–3265

    CAS  PubMed  Google Scholar 

  • Sonawane M, Martin-Maischein H, Schwarz H, Nusslein-Volhard C (2009) Lgl2 and E-cadherin act antagonistically to regulate hemidesmosome formation during epidermal development in zebrafish. Development 136(8):1231–1240. doi:10.1242/dev.032508, dev.032508 [pii]

    CAS  PubMed  Google Scholar 

  • Sotelo NS, Valiente M, Gil A, Pulido R (2012) A functional network of the tumor suppressors APC, hDlg, and PTEN, that relies on recognition of specific PDZ-domains. J Cell Biochem 113(8):2661–2670. doi:10.1002/jcb.24141

    CAS  PubMed  Google Scholar 

  • Sripathy S, Lee M, Vasioukhin V (2011) Mammalian Llgl2 is necessary for proper branching morphogenesis during placental development. Mol Cell Biol 31(14):2920–2933. doi:10.1128/MCB.05431-11, MCB.05431-11 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • St Johnston D, Ahringer J (2010) Cell polarity in eggs and epithelia: parallels and diversity. Cell 141(5):757–774. doi:10.1016/j.cell.2010.05.011, S0092-8674(10)00547-7 [pii]

    CAS  PubMed  Google Scholar 

  • Staples J, Broadie K (2013) The cell polarity scaffold Lethal Giant Larvae regulates synapse morphology and function. J Cell Sci 126(Pt 9):1992–2003. doi:10.1242/jcs.120139

    PubMed Central  CAS  PubMed  Google Scholar 

  • Stephenson LM, Sammut B, Graham DB, Chan-Wang J, Brim KL, Huett AS, Miletic AV, Kloeppel T, Landry A, Xavier R, Swat W (2007) DLGH1 is a negative regulator of T-lymphocyte proliferation. Mol Cell Biol 27(21):7574–7581

    PubMed Central  CAS  PubMed  Google Scholar 

  • Stiffler MA, Chen JR, Grantcharova VP, Lei Y, Fuchs D, Allen JE, Zaslavskaia LA, MacBeath G (2007) PDZ domain binding selectivity is optimized across the mouse proteome. Science 317(5836):364–369. doi:10.1126/science.1144592

    PubMed Central  CAS  PubMed  Google Scholar 

  • Stirnimann CU, Petsalaki E, Russell RB, Muller CW (2010) WD40 proteins propel cellular networks. Trends Biochem Sci 35(10):565–574. doi:10.1016/j.tibs.2010.04.003

    CAS  PubMed  Google Scholar 

  • Stottmann RW, Moran JL, Turbe-Doan A, Driver E, Kelley M, Beier DR (2011) Focusing forward genetics: a tripartite ENU screen for neurodevelopmental mutations in the mouse. Genetics 188(3):615–624. doi:10.1534/genetics.111.126862, genetics.111.126862 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Strand D, Jakobs R, Merdes G, Neumann B, Kalmes A, Heid HW, Husmann I, Mechler BM (1994) The Drosophila lethal(2)giant larvae tumor suppressor protein forms homo-oligomers and is associated with nonmuscle myosin II heavy chain. J Cell Biol 127(5):1361–1373

    CAS  PubMed  Google Scholar 

  • Strand D, Unger S, Corvi R, Hartenstein K, Schenkel H, Kalmes A, Merdes G, Neumann B, Krieg-Schneider F, Coy JF et al (1995) A human homologue of the Drosophila tumour suppressor gene l(2)gl maps to 17p11.2-12 and codes for a cytoskeletal protein that associates with nonmuscle myosin II heavy chain. Oncogene 11(2):291–301

    CAS  PubMed  Google Scholar 

  • Su WH, Mruk DD, Wong EW, Lui WY, Cheng CY (2012) Polarity protein complex Scribble/Lgl/Dlg and epithelial cell barriers. Adv Exp Med Biol 763:149–170

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sun Y, Aiga M, Yoshida E, Humbert PO, Bamji SX (2009) Scribble interacts with beta-catenin to localize synaptic vesicles to synapses. Mol Biol Cell 20(14):3390–3400. doi:10.1091/mbc.E08-12-1172

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sun Y, Bamji SX (2011) Beta-Pix modulates actin-mediated recruitment of synaptic vesicles to synapses. J Neurosci 31(47):17123–17133. doi:10.1523/JNEUROSCI.2359-11.2011

    CAS  PubMed  Google Scholar 

  • Takizawa S, Nagasaka K, Nakagawa S, Yano T, Nakagawa K, Yasugi T, Takeuchi T, Kanda T, Huibregtse JM, Akiyama T, Taketani Y (2006) Human scribble, a novel tumor suppressor identified as a target of high-risk HPV E6 for ubiquitin-mediated degradation, interacts with adenomatous polyposis coli. Genes Cells 11(4):453–464

    CAS  PubMed  Google Scholar 

  • Tamori Y, Bialucha CU, Tian AG, Kajita M, Huang YC, Norman M, Harrison N, Poulton J, Ivanovitch K, Disch L, Liu T, Deng WM, Fujita Y (2010) Involvement of Lgl and Mahjong/VprBP in cell competition. PLoS Biol 8(7):e1000422

    PubMed Central  PubMed  Google Scholar 

  • Tamori Y, Deng WM (2013) Tissue repair through cell competition and compensatory cellular hypertrophy in postmitotic epithelia. Dev Cell 25(4):350–363. doi:10.1016/j.devcel.2013.04.013, S1534-5807(13)00242-6 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tarpey P, Parnau J, Blow M, Woffendin H, Bignell G, Cox C, Cox J, Davies H, Edkins S, Holden S, Korny A, Mallya U, Moon J, O’Meara S, Parker A, Stephens P, Stevens C, Teague J, Donnelly A, Mangelsdorf M, Mulley J, Partington M, Turner G, Stevenson R, Schwartz C, Young I, Easton D, Bobrow M, Futreal PA, Stratton MR, Gecz J, Wooster R, Raymond FL (2004) Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation. Am J Hum Genet 75(2):318–324

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tay HG, Schulze SK, Compagnon J, Foley FC, Heisenberg CP, Yost HJ, Abdelilah-Seyfried S, Amack JD (2013) Lethal giant larvae 2 regulates development of the ciliated organ Kupffer’s vesicle. Development 140(7):1550–1559. doi:10.1242/dev.087130

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tonikian R, Zhang Y, Sazinsky SL, Currell B, Yeh JH, Reva B, Held HA, Appleton BA, Evangelista M, Wu Y, Xin X, Chan AC, Seshagiri S, Lasky LA, Sander C, Boone C, Bader GD, Sidhu SS (2008) A specificity map for the PDZ domain family. PLoS Biol 6(9):e239. doi:10.1371/journal.pbio.0060239, 07-PLBI-RA-4212 [pii]

    PubMed Central  PubMed  Google Scholar 

  • Uhlirova M, Bohmann D (2006) JNK- and Fos-regulated Mmp1 expression cooperates with Ras to induce invasive tumors in Drosophila. EMBO J 25(22):5294–5304

    PubMed Central  CAS  PubMed  Google Scholar 

  • Uhlirova M, Jasper H, Bohmann D (2005) Non-cell-autonomous induction of tissue overgrowth by JNK/Ras cooperation in a Drosophila tumor model. Proc Natl Acad Sci U S A 102(37):13123–13128

    PubMed Central  CAS  PubMed  Google Scholar 

  • Vaira V, Faversani A, Dohi T, Maggioni M, Nosotti M, Tosi D, Altieri DC, Bosari S (2011) Aberrant overexpression of the cell polarity module scribble in human cancer. Am J Pathol 178:2478–2483

    PubMed Central  CAS  PubMed  Google Scholar 

  • Vaira V, Faversani A, Dohi T, Montorsi M, Augello C, Gatti S, Coggi G, Altieri DC, Bosari S (2012) miR-296 regulation of a cell polarity-cell plasticity module controls tumor progression. Oncogene 31(1):27–38. doi:10.1038/onc.2011.209, onc2011209 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Van Campenhout CA, Eitelhuber A, Gloeckner CJ, Giallonardo P, Gegg M, Oller H, Grant SG, Krappmann D, Ueffing M, Lickert H (2011) Dlg3 trafficking and apical tight junction formation is regulated by nedd4 and nedd4-2 e3 ubiquitin ligases. Dev Cell 21(3):479–491. doi:10.1016/j.devcel.2011.08.003, S1534-5807(11)00315-7 [pii]

    PubMed  Google Scholar 

  • Varelas X, Samavarchi-Tehrani P, Narimatsu M, Weiss A, Cockburn K, Larsen BG, Rossant J, Wrana JL (2010) The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-beta-SMAD pathway. Dev Cell 19(6):831–844. doi:10.1016/j.devcel.2010.11.012, S1534-5807(10)00539-3 [pii]

    CAS  PubMed  Google Scholar 

  • Verghese S, Waghmare I, Kwon H, Hanes K, Kango-Singh M (2012) Scribble acts in the Drosophila fat-hippo pathway to regulate warts activity. PLoS One 7(11):e47173. doi:10.1371/journal.pone.0047173, PONE-D-12-25889 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Vermeer PD, Einwalter LA, Moninger TO, Rokhlina T, Kern JA, Zabner J, Welsh MJ (2003) Segregation of receptor and ligand regulates activation of epithelial growth factor receptor. Nature 422(6929):322–326

    CAS  PubMed  Google Scholar 

  • von Stein W, Ramrath A, Grimm A, Muller-Borg M, Wodarz A (2005) Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling. Development 132(7):1675–1686

    Google Scholar 

  • Wada H, Iwasaki M, Sato T, Masai I, Nishiwaki Y, Tanaka H, Sato A, Nojima Y, Okamoto H (2005) Dual roles of zygotic and maternal Scribble1 in neural migration and convergent extension movements in zebrafish embryos. Development 132(10):2273–2285

    CAS  PubMed  Google Scholar 

  • Walsh GS, Grant PK, Morgan JA, Moens CB (2011) Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration. Development 138(14):3033–3042. doi:10.1242/dev.063842, 138/14/3033 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, Nord AS, Kusenda M, Malhotra D, Bhandari A, Stray SM, Rippey CF, Roccanova P, Makarov V, Lakshmi B, Findling RL, Sikich L, Stromberg T, Merriman B, Gogtay N, Butler P, Eckstrand K, Noory L, Gochman P, Long R, Chen Z, Davis S, Baker C, Eichler EE, Meltzer PS, Nelson SF, Singleton AB, Lee MK, Rapoport JL, King MC, Sebat J (2008) Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320(5875):539–543. doi:10.1126/science.1155174

    CAS  PubMed  Google Scholar 

  • Wan Q, Liu J, Zheng Z, Zhu H, Chu X, Dong Z, Huang S, Du Q (2012) Regulation of myosin activation during cell-cell contact formation by Par3-Lgl antagonism: entosis without matrix detachment. Mol Biol Cell 23(11):2076–2091. doi:10.1091/mbc.E11-11-0940, mbc.E11-11-0940 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wang S, Watanabe T, Matsuzawa K, Katsumi A, Kakeno M, Matsui T, Ye F, Sato K, Murase K, Sugiyama I, Kimura K, Mizoguchi A, Ginsberg MH, Collard JG, Kaibuchi K (2012) Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration. J Cell Biol 199(2):331–345. doi:10.1083/jcb.201202041, jcb.201202041 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wang T, Liu Y, Xu XH, Deng CY, Wu KY, Zhu J, Fu XQ, He M, Luo ZG (2011) Lgl1 activation of rab10 promotes axonal membrane trafficking underlying neuronal polarization. Dev Cell 21(3):431–444. doi:10.1016/j.devcel.2011.07.007, S1534-5807(11)00299-1 [pii]

    CAS  PubMed  Google Scholar 

  • Wansleeben C, van Gurp L, Feitsma H, Kroon C, Rieter E, Verberne M, Guryev V, Cuppen E, Meijlink F (2011) An ENU-mutagenesis screen in the mouse: identification of novel developmental gene functions. PLoS One 6(4):e19357. doi:10.1371/journal.pone.0019357, 10-PONE-RA-20961 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Warner SJ, Yashiro H, Longmore GD (2010) The Cdc42/Par6/aPKC Polarity Complex Regulates Apoptosis-Induced Compensatory Proliferation in Epithelia. Curr Biol 20:677–686

    PubMed Central  CAS  PubMed  Google Scholar 

  • Warzecha CC, Jiang P, Amirikian K, Dittmar KA, Lu H, Shen S, Guo W, Xing Y, Carstens RP (2010) An ESRP-regulated splicing programme is abrogated during the epithelial-mesenchymal transition. EMBO J 29(19):3286–3300. doi:10.1038/emboj.2010.195

    PubMed Central  CAS  PubMed  Google Scholar 

  • Waterhouse RM, Tegenfeldt F, Li J, Zdobnov EM, Kriventseva EV (2013) OrthoDB: a hierarchical catalog of animal, fungal and bacterial orthologs. Nucleic Acids Res 41(Database issue):D358–D365. doi:10.1093/nar/gks1116

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wells J, Rivera MN, Kim WJ, Starbuck K, Haber DA (2010) The predominant WT1 isoform (+KTS) encodes a DNA-binding protein targeting the planar cell polarity gene Scribble in renal podocytes. Mol Cancer Res 8(7):975–985. doi:10.1158/1541-7786.MCR-10-0033, 1541-7786.MCR-10-0033 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wigerius M, Asghar N, Melik W, Johansson M (2013) Scribble controls NGF-mediated neurite outgrowth in PC12 cells. Eur J Cell Biol 92(6–7):213–221. doi:10.1016/j.ejcb.2013.07.002, S0171-9335(13)00048-4 [pii]

    CAS  PubMed  Google Scholar 

  • Willecke M, Toggweiler J, Basler K (2011) Loss of PI3K blocks cell-cycle progression in a Drosophila tumor model. Oncogene 30(39):4067–4074. doi:10.1038/onc.2011.125, onc2011125 [pii]

    CAS  PubMed  Google Scholar 

  • Willoughby LF, Schlosser T, Manning SA, Parisot JP, Street IP, Richardson HE, Humbert PO, Brumby AM (2012) An in vivo large-scale chemical screening platform using Drosophila for anti-cancer drug discovery. Dis Model Mech. doi:10.1242/dmm.009985

    PubMed Central  PubMed  Google Scholar 

  • Wirtz-Peitz F, Nishimura T, Knoblich JA (2008) Linking cell cycle to asymmetric division: Aurora-A phosphorylates the PAR complex to regulate Numb localization. Cell 135(1):161–173. doi:10.1016/j.cell.2008.07.049, S0092-8674(08)01024-6 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Woods DF, Bryant PJ (1989) Molecular cloning of the lethal(1)discs large-1 oncogene of Drosophila. Dev Biol 134(1):222–235

    CAS  PubMed  Google Scholar 

  • Wu WJ, Tu S, Cerione RA (2003) Activated Cdc42 sequesters c-Cbl and prevents EGF receptor degradation. Cell 114(6):715–725, doi:S0092867403006883 [pii]

    CAS  PubMed  Google Scholar 

  • Xavier R, Rabizadeh S, Ishiguro K, Andre N, Ortiz JB, Wachtel H, Morris DG, Lopez-Ilasaca M, Shaw AC, Swat W, Seed B (2004) Discs large (Dlg1) complexes in lymphocyte activation. J Cell Biol 166(2):173–178

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yamanaka T, Ohno S (2008) Role of Lgl/Dlg/Scribble in the regulation of epithelial junction, polarity and growth. Front Biosci 13:6693–6707

    CAS  PubMed  Google Scholar 

  • Yamben IF, Rachel RA, Shatadal S, Copeland NG, Jenkins NA, Warming S, Griep AE (2013) Scrib is required for epithelial cell identity and prevents epithelial to mesenchymal transition in the mouse. Dev Biol 384(1):41–52. doi:10.1016/j.ydbio.2013.09.027, S0012-1606(13)00513-7 [pii]

    CAS  PubMed  Google Scholar 

  • Yan J, Lu Q, Fang X, Adler PN (2009) Rho1 has multiple functions in Drosophila wing planar polarity. Dev Biol 333(1):186–199

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yates LL, Schnatwinkel C, Hazelwood L, Chessum L, Paudyal A, Hilton H, Romero MR, Wilde J, Bogani D, Sanderson J, Formstone C, Murdoch JN, Niswander LA, Greenfield A, Dean CH (2013) Scribble is required for normal epithelial cell-cell contacts and lumen morphogenesis in the mammalian lung. Dev Biol 373(2):267–280. doi:10.1016/j.ydbio.2012.11.012, S0012-1606(12)00631-8 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yin G, Haendeler J, Yan C, Berk BC (2004) GIT1 functions as a scaffold for MEK1-extracellular signal-regulated kinase 1 and 2 activation by angiotensin II and epidermal growth factor. Mol Cell Biol 24(2):875–885

    PubMed Central  CAS  PubMed  Google Scholar 

  • Young LC, Hartig N, Munoz-Alegre M, Oses-Prieto JA, Durdu S, Bender S, Vijayakumar V, Vietri Rudan M, Gewinner C, Henderson S, Jathoul AP, Ghatrora R, Lythgoe MF, Burlingame AL, Rodriguez-Viciana P (2013) An MRAS, SHOC2, and SCRIB complex coordinates ERK pathway activation with polarity and tumorigenic growth. Mol Cell 52(5):679–692. doi:10.1016/j.molcel.2013.10.004, S1097-2765(13)00745-4 [pii]

    CAS  PubMed  Google Scholar 

  • Zarbalis K, May SR, Shen Y, Ekker M, Rubenstein JL, Peterson AS (2004) A focused and efficient genetic screening strategy in the mouse: identification of mutations that disrupt cortical development. PLoS Biol 2(8):E219

    PubMed Central  PubMed  Google Scholar 

  • Zeitler J, Hsu CP, Dionne H, Bilder D (2004) Domains controlling cell polarity and proliferation in the Drosophila tumor suppressor Scribble. J Cell Biol 167(6):1137–1146

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zeniou-Meyer M, Liu Y, Begle A, Olanich ME, Hanauer A, Becherer U, Rettig J, Bader MF, Vitale N (2008) The Coffin-Lowry syndrome-associated protein RSK2 is implicated in calcium-regulated exocytosis through the regulation of PLD1. Proc Natl Acad Sci U S A 105(24):8434–8439. doi:10.1073/pnas.0710676105, 0710676105 [pii]

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang H, Macara IG (2006) The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis. Nat Cell Biol 8(3):227–237

    CAS  PubMed  Google Scholar 

  • Zhang X, Wang P, Gangar A, Zhang J, Brennwald P, TerBush D, Guo W (2005) Lethal giant larvae proteins interact with the exocyst complex and are involved in polarized exocytosis. J Cell Biol 170(2):273–283

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang Y, Guo H, Kwan H, Wang JW, Kosek J, Lu B (2007) PAR-1 kinase phosphorylates Dlg and regulates its postsynaptic targeting at the Drosophila neuromuscular junction. Neuron 53(2):201–215. doi:10.1016/j.neuron.2006.12.016

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zhao M, Szafranski P, Hall CA, Goode S (2008) Basolateral junctions utilize warts signaling to control epithelial-mesenchymal transition and proliferation crucial for migration and invasion of Drosophila ovarian epithelial cells. Genetics 178(4):1947–1971. doi:10.1534/genetics.108.086983

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zhu J, Shang Y, Wan Q, Xia Y, Chen J, Du Q, Zhang M (2014) Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl. Cell Res 24(4):451–463. doi:10.1038/cr.2014.16

    CAS  PubMed  Google Scholar 

  • Zigman M, le Trinh A, Fraser SE, Moens CB (2011) Zebrafish neural tube morphogenesis requires Scribble-dependent oriented cell divisions. Curr Biol 21(1):79–86. doi:10.1016/j.cub.2010.12.005

    PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Marta Portela for critical reading of the manuscript. P.O.H., S.R., and H.E.R. were supported from funding from the ARC and NHMRC of Australia.

Author information

Authors and Affiliations

  1. Cell Cycle and Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, Locked Bag 1, A’Beckett Street, Melbourne, VIC, 8006, Australia

    Patrick O. Humbert & Lorey Smith

  2. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia

    Patrick O. Humbert, Sarah M. Russell & Helena E. Richardson

  3. Department of Pathology, The University of Melbourne, Parkville, Australia

    Patrick O. Humbert, Sarah M. Russell & Lorey Smith

  4. Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Australia

    Patrick O. Humbert & Helena E. Richardson

  5. Immune Signalling Laboratory, Peter MacCallum Cancer Centre, Locked Bag 1, A’Beckett Street, Melbourne, VIC, 8006, Australia

    Sarah M. Russell

  6. Centre for Micro-Photonics, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Australia

    Sarah M. Russell

  7. Cell Cycle and Development Laboratory, Peter MacCallum Cancer Centre, Locked Bag 1, A’Beckett Street, Melbourne, VIC, 8006, Australia

    Helena E. Richardson

  8. Department of Anatomy and Cell Biology, The University of Melbourne, Parkville, Australia

    Helena E. Richardson

Authors
  1. Patrick O. Humbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah M. Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lorey Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Helena E. Richardson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrick O. Humbert .

Editor information

Editors and Affiliations

  1. Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation (ZMBE), University Münster, Münster, Nordrhein-Westfalen, Germany

    Klaus Ebnet

Glossary

Scrib

Scribble

Dlg

Discs large

Lgl

Lethal giant larvae

AB

Apical–basal

FR

Front–rear

ACD

Asymmetric cell division

PCP

Planar cell polarity

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Humbert, P.O., Russell, S.M., Smith, L., Richardson, H.E. (2015). The Scribble–Dlg–Lgl Module in Cell Polarity Regulation. In: Ebnet, K. (eds) Cell Polarity 1. Springer, Cham. https://doi.org/10.1007/978-3-319-14463-4_4

Download citation

Publish with us

Policies and ethics

Search

Navigation