Skip to main content

Advertisement

SpringerLink
Log in

The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system

  • Molecular and Genomic Physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Inositol Inpp5k (or Pps, SKIP) is a member of the inositol polyphosphate 5-phosphatases family with a poorly characterized function in vivo. In this study, we explored the function of this inositol 5-phosphatase in mice and cells overexpressing the 42-kDa mouse Inpp5k protein. Inpp5k transgenic mice present defects in water metabolism characterized by a reduced plasma osmolality at baseline, a delayed urinary water excretion following a water load, and an increased acute response to vasopressin. These defects are associated with the expression of the Inpp5k transgene in renal collecting ducts and with alterations in the arginine vasopressin/aquaporin-2 signalling pathway in this tubular segment. Analysis in a mouse collecting duct mCCD cell line revealed that Inpp5k overexpression leads to increased expression of the arginine vasopressin receptor type 2 and increased cAMP response to arginine vasopressin, providing a basis for increased aquaporin-2 expression and plasma membrane localization with increased osmotically induced water transport. Altogether, our results indicate that Inpp5k 5-phosphatase is important for the control of the arginine vasopressin/aquaporin-2 signalling pathway and water transport in kidney collecting ducts.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Arhabi AH, Terryn S, Valenti G, Caron N, Serradeil-Le Gal C, Raufaste D, Nielsen S, Horie S, Verbavatz JM, Devuyst O (2007) PKD1 haploinsufficiency causes a syndrome of inappropriate antidiuresis in mice. J Am Soc Nephrol 18:1740–1753

    Article  Google Scholar 

  2. Astle MV, Seaton G, Davies EM, Fedele CG, Rahman P, Arsala L, Mitchell CA (2006) Regulation of phosphoinosotide signaling by the inositol polyphosphate 5-phosphatases. IUBMB Life 58:451–456

    Article  PubMed  CAS  Google Scholar 

  3. Astle MV, Horan KA, Ooms LM, Mitchell CA (2007) The inositol polyphosphate 5-phosphatases: traffic controllers, waistline watchers and tumor suppressors? Biochem Soc Symp 12:2836–2848

    Google Scholar 

  4. Barlow CA, Laishram RS, Anderson RA (2010) Nuclear phosphoinositides: a signaling enigma wrapped in a compartmental conundrum. Trends Cell Biol 20:25–35

    Article  PubMed  CAS  Google Scholar 

  5. Belge H, Gailly P, Schwaller B, Loffing J, Debaix H, Riveira-Munoz E, Beauwens R, Devogelaer JP, Hoendero JG, Bindels RJ, Devuyst O (2007) Renal expression of parvalbumin is critical for NaCl handling and response to diuretics. Proc Natl Acad Sci USA 104:14849–14854

    Article  PubMed  CAS  Google Scholar 

  6. Bielas SL, Silhavy JL, Brancati F, Kisseleva MV, Al-Gazali L, Sztriha L, Bayoumi RA, Zaki MS, Abdel-Aleem A, Rosti O, Kayserili H, Swistun D, Scott LC, Bertini E, Boltshauser E, Fazzi E, Travaglini L, Field SJ, Gayral S, Jacoby M, Schurmans S, Dallapiccola B, Majerus PW, Valente EM, Gleeson JG (2009) Mutations in the inositol polyphosphate-5-phosphatase E gene link phosphatidylinositol signaling to the ciliopathies. Nature Genetics 41:1032–1036

    Article  PubMed  CAS  Google Scholar 

  7. Blero D, Payrastre B, Schurmans S, Erneux C (2007) Phosphoinositide phosphatases in a network of signaling reactions. Pflug Arch Eur J Phys 455:31–44

    Article  CAS  Google Scholar 

  8. Christensen BM, Zelenina M, Aperia A, Nielsen S (2000) Localization and regulation of PKA-phosphorylated AQP2 in response to V2-receptor agonist/antagonist treatment. Am J Physiol Renal Physiol 278:F29–F42

    PubMed  CAS  Google Scholar 

  9. Christensen EI, Devuyst O, Dom G, Nielsen R, Van der Smissen P, Verroust P, Leruth M, Guggino WB, Courtoy PJ (2003) Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. Proc Natl Acad Sci USA 100:8472–8477

    Article  PubMed  CAS  Google Scholar 

  10. Clément S, Krause U, Desmedt F, Tanti JF, Behrends J, Pesesse X, Sasaki T, Penninger J, Doherty M, Malaisse W, Dumont JE, Le Marchand-Brustel Y, Erneux C, Hue L, Schurmans S (2001) The lipid phosphatase SHIP2 controls insulin sensitivity. Nature 409:92–96

    Article  PubMed  Google Scholar 

  11. Communi D, Lecocq R, Erneux C (1996) Arginine 343 and 350 are two active residues involved in substrate binding by human type 1 d-myo-inositol 1,4,5-trisphosphate 5-phosphatase. J Biol Chem 271:11676–11683

    Article  PubMed  CAS  Google Scholar 

  12. Di Paolo G, De Camilli P (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature 443:651–657

    Article  PubMed  Google Scholar 

  13. Downes CP, Gray A, Lucocq JM (2005) Probing phosphoinositide functions in signalling and membrane trafficking. Trends Cell Biol 15:259–268

    Article  PubMed  CAS  Google Scholar 

  14. Gaeggeler HP, Gonzalez-Rodriguez E, Jaeger NF, Loffing-Cueni D, Norregaard R, Loffing J, Horisberger JD, Rossier BC (2005) Mineralocorticoid versus glucocorticoid receptor occupancy mediating aldosteronestimulated sodium transport in a novel renal cell line. J Am Soc Nephrol 16:878–889

    Article  PubMed  CAS  Google Scholar 

  15. Gaeggeler HP, Guillod Y, Loffing-Cueni D, Loffing J, Rossier BC (2010) Vasopressin-dependent coupling between sodium transport and water flow in a mouse cortical collecting duct cell line. Kidney Int, Dec 22, Epub ahead of print.

  16. Gurung R, Tan A, Ooms LM, McGrath MJ, Huysmans RD, Munday AD, Prescott M, Whisstock JC, Mitchell CA (2003) Identification of a novel domain in two mammalian inositol-polyphosphate 5-phosphatases that mediates membrane ruffle localization. J Biol Chem 278:11376–11385

    Article  PubMed  CAS  Google Scholar 

  17. Halstead JR, Jalink K, Divecha N (2005) An emerging role for PtdIns(4,5)P2-mediated signalling in human disease. Trends Pharmacol Sci 26:654–660

    Article  PubMed  CAS  Google Scholar 

  18. Heo WD, Inoue T, Park WS, Kim ML, Park BO, Wandless TJ, Meyer T (2006) PI(3,4,5)P3 and PI(4,5)P2 lipid target proteins with polybasic clusters to the plasma membrane. Science 314:1458–1461

    Article  PubMed  CAS  Google Scholar 

  19. Ijuin T, Mochizuki Y, Fukami K, Funaki M, Asano T, Takenawa T (2000) Identification and characterization of a novel inositol polyphosphate 5-phosphatase. J Biol Chem 275:10870–10875

    Article  PubMed  CAS  Google Scholar 

  20. Ijuin T, Takenawa T (2003) SKIP negatively regulates insulin-induced GLUT4 translocation and membrane ruffle formation. Mol Cell Biol 23:1209–1220

    Article  PubMed  CAS  Google Scholar 

  21. Ijuin T, Yu YE, Mizutani K, Pao A, Tateya S, Tamori Y, Bradley A, Takenawa T (2008) Increased insulin action in SKIP heterozygous knockout mice. Mol Cell Biol 28:5184–5195

    Article  PubMed  CAS  Google Scholar 

  22. Jacoby M, Cox JJ, Gayral S, Hampshire DJ, Ayub M, Blockmans M, Pernot E, Kisseleva MV, Compère P, Schiffmann SN, Gergely F, Riley JH, Pérez-Morga D, Woods GC, Schurmans S (2009) INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse. Nat Genet 41:1027–1031

    Article  PubMed  CAS  Google Scholar 

  23. Jänne PA, Suchy SF, Bernard D, McDonald M, Crawley J, Grinberg A, Wynshaw-Boris A, Westphal H, Nussbaum RL (1998) Functional overlap between murine Inpp 5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice. J Clin Invest 101:2042–2053

    Article  PubMed  Google Scholar 

  24. Jouret F, Bernard A, Hermans C, Dom G, Terryn S, Leal T, Lebecque P, Cassiman JJ, Scholte BJ, de Jonge HR, Courtoy PJ, Devuyst O (2007) Cystic fibrosis is associated with a defect in apical receptor-mediated endocytosis in mouse and human kidney. J Am Soc Nephrol 18:707–718

    Article  PubMed  CAS  Google Scholar 

  25. Kagawa S, Soeda Y, Ishihara H, Oya T, Sasahara M, Yaguchi S, Oshita R, Wada T, Tsuneki H, Sasaoka T (2008) Impact of transgenic overexpression of SH2-containing inositol 5′-phosphatase 2 on glucose metabolism and insulin signalling in mice. Endocrinology 149:642–650

    Article  PubMed  CAS  Google Scholar 

  26. Kaisaki PJ, Delépine M, Woon PY, Sebag-Montefiore L, Wilder SP, Menzel S, Vionnet N, Marion E, Riveline JP, Charpentier G, Schurmans S, Levy JC, Lathrop M, Farrall M, Gauguier D (2004) Polymorphisms in type-II SH2 domain-containing inositol 5-phosphatase (INPPL1, SHIP2) are associated with physiological abnormalities of the metabolic syndrome. Diabetes 53:1900–1904

    Article  PubMed  CAS  Google Scholar 

  27. Keune WJ, Boultsma Y, Sommer L, Jones D, Divecha N (2010) Phosphoinositide signaling in the nucleus. Adv Enzyme Regul, Oct. 28, Epub ahead of print.

  28. Lemmon MA (2008) Membrane recognition by phospholipid-binding domains. Nat Rev Mol Cell Biol 9:99–111

    Article  PubMed  CAS  Google Scholar 

  29. Ling K, Schill NJ, Wagoner MP, Sun Y, Anderson RA (2006) Movin’ on up: the role of PtdIns(4,5)P2 in cell migration. Trends Cell Biol 16:276–284

    Article  PubMed  CAS  Google Scholar 

  30. Liu Y, Bankaitis VA (2010) Phosphoinositide phosphatases in cell biology and diseases. Prog Lipid Res 49:201–217

    Article  PubMed  CAS  Google Scholar 

  31. Marion E, Kaisaki P, Pouillon V, Gueydan C, Levy JC, Bodson A, Krzentowski G, Daubresse JC, Mockel J, Behrends J, Servais G, Szpirer C, Kruys V, Gauguier D, Schurmans S (2002) The gene INPPL1, encoding the lipid phosphatase SHIP2, is a candidate for type 2 diabetes in rat and man. Diabetes 51:2012–2017

    Article  PubMed  CAS  Google Scholar 

  32. McCrea HJ, De Camilli P (2009) Mutations in phosphoinositide metabolizing enzymes and human disease. Physiology (Bethesda) 24:8–16

    Article  CAS  Google Scholar 

  33. Ooms LM, Horan KA, Rahman P, Seaton G, Gurung R, Kathesparan DS, Mitchell CA (2009) The role of the inositol polyphosphate 5-phosphatases in cellular function and human disease. Biochem J 419:29–49

    Article  PubMed  CAS  Google Scholar 

  34. Sleeman MW, Wortley KE, Lai KMV, Gowen LC, Kintner J, Kline WO, Garcia K, Stitt TN, Yancopoulos GD, Wiegand SJ, Glass DJ (2005) Absence of the lipid phosphatise SHIP2 confers resistance to dietary obesity. Nat Med 11:199–205

    Article  PubMed  CAS  Google Scholar 

  35. Suh BC, Hille B (2005) Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate. Curr Opin Neurobiol 15:370–378

    Article  PubMed  CAS  Google Scholar 

  36. Trebak M, Lemonnier L, Dehaven WI, Wedel BJ, Bird GS, Putney JW Jr (2009) Complex functions of phosphatidylinositol 4,5-bisphosphate in regulation of TRPC5 cation channels. Pflugers Arch 457:757–769

    Article  PubMed  CAS  Google Scholar 

  37. Vandeput F, Backers K, Villeret V, Pesesse X, Erneux C (2006) The influence of anionic lipids on SHIP2 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase activity. Cell Signal 18:2193–2199

    Article  PubMed  CAS  Google Scholar 

  38. Wada T, Sasaoka T, Funaki M, Hori H, Murakami S, Ishiki M, Haruta Y, Asano T, Ogawa W, Ishihara H, Kobayashi M (2001) Overexpression of SH2-containing inositol phosphatise 2 results in negative regulation of insulin-induced metabolic actions in 3T3-L1 adipocytes via its 5′-phosphatase catalytic activity. Mol Cell Biol 21:1633–1646

    Article  PubMed  CAS  Google Scholar 

  39. Xiong Q, Deng CY, Chai J, Jiang SW, Xiong YZ, Li FE, Zheng R (2009) Knockdown of endogenous SKIP gene enhanced insulin-induced glycogen synthesis signalling in differentiating C2C12 myoblasts. BMB Rep 42:119–124

    Article  PubMed  CAS  Google Scholar 

  40. Yu H, Fukami K, Watanabe Y, Ozaki C, Takenawa T (1998) Phosphatidylinositol 4,5-bisphosphate reverses the inhibition of RNA transcription caused by histone H1. Eur J Biochem 251:281–287

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Y. Maréchal (IRIBHM, IBMM), A. Ahrabi and H. Belge (Division of Nephrology, UCL) for discussions, C. Moreau (IRIBHM), H. Debaix, V. Beaujean and Y. Cnops (Division of Nephrology, UCL) for technical assistance, and D. Trono (Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland) for lentiviral reagents. This work was supported by the Fonds de la Recherche Scientifique-FNRS (FRS-FNRS)(to V.P., S.S., C.E. and O.D.), the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA)(fellowships to E.P., M.B. and M.J.), the Fonds de la Recherche Scientifique Médicale (FRSM) (to S.S., C.E. and O.D.), the Fonds David et Alice Van Buuren (to M.J.), the Fondation Rose et Jean Hoguet (to E.P.), and a Concerted Research Action (05/10-328), The Chaire Spadel “Eau et Santé” at the UCL (O.D.), an Inter-University Attraction Pole (IUAP P6/05 to O.D.; IUAP P6/28 to C.E.), the NCCR Kidney CH program of the Swiss National Science Foundation and the EUNEFRON project of the European Community (FP7) to O.D.

Author information

Author notes

  1. Olivier Devuyst

    Present address: Institute of Physiology, Zurich Centre for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland

  2. Stéphane Schurmans

    Present address: Laboratoire de Génétique Fonctionnelle, GIGA-Research Centre/B34, Avenue de l’Hôpital 1, 4000, Liège, Belgium

Authors and Affiliations

  1. Institut de Recherches Interdisciplinaires en Biologie Humaine et Moléculaire (IRIBHM), Brussels, Belgium

    Eileen Pernot, Siew Chiat Cheong, Marianne Blockmans, Monique Jacoby, Valérie Pouillon, Stéphanie Gayral, Christophe Erneux & Stéphane Schurmans

  2. Institut de Biologie et de Médecine Moléculaires (IBMM), Gosselies, Belgium

    Eileen Pernot, Siew Chiat Cheong, Marianne Blockmans, Monique Jacoby, Valérie Pouillon, Stéphanie Gayral & Stéphane Schurmans

  3. Division of Nephrology, Université catholique de Louvain Medical School, Brussels, Belgium

    Sara Terryn, Sylvie Janas & Olivier Devuyst

  4. Laboratoire de Physiologie Cellulaire et Moléculaire, Faculté de Médecine, Université Libre de Bruxelles, Brussels, Belgium

    Nicolas Markadieu & Renaud Beauwens

  5. Département de Pharmacologie et de Toxicologie, Université de Lausanne, Lausanne, Switzerland

    Bernard C. Rossier

  6. Secteur de Biochimie Métabolique, Département des Sciences Fonctionnelles, Faculté de Médecine-Vétérinaire, Université de Liège, 4000, Liège, Belgium

    Stéphane Schurmans

Authors
  1. Eileen Pernot
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Terryn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Siew Chiat Cheong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicolas Markadieu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sylvie Janas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marianne Blockmans
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Monique Jacoby
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Valérie Pouillon
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stéphanie Gayral
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Bernard C. Rossier
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Renaud Beauwens
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Christophe Erneux
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Olivier Devuyst
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Stéphane Schurmans
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Olivier Devuyst or Stéphane Schurmans.

Additional information

Eileen Pernot, Sara Terryn, Olivier Devuyst and Stéphane Schurmans contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Table 1

Primers sequences (DOC 35 kb)

Supplementary Table 2

Baseline parameters, renal function and water metabolism in Inpp5k transgenic mice (DOC 28 kb)

Supplementary Information

(DOC 28 kb)

Supplementary Figure Legends

(DOC 24.5 kb)

Supplementary Figure 1

(PDF 158 kb)

Supplementary Figure 2

(PDF 78.9 kb)

Supplementary Figure 3

(PDF 136 kb)

Supplementary Figure 4

(PDF 57.6 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pernot, E., Terryn, S., Cheong, S.C. et al. The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system. Pflugers Arch - Eur J Physiol 462, 871–883 (2011). https://doi.org/10.1007/s00424-011-1028-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-011-1028-0

Keywords

Search

Navigation