Abstract
Recruitment of oligodendrocyte precursor cells (OPCs) to the lesions is the most important event for remyelination after central nervous system (CNS) injury or in demyelinating diseases. However, the underlying molecular mechanism is not fully understood. In the present study, we found high concentrations of ATP could increase the number of migrating OPCs in vitro, while after pretreatment with oxidized ATP (a P2X7 receptor antagonist), the promotive effect was attenuated. The promotive effect of 2′(3′)-O-(4-benzoylbenzoyl) adenosine 5′-triphosphate (BzATP) (a P2X7 receptor agonist) was more potent than ATP. After incubation with BzATP, the activity of Fyn, one member of the Src family of kinases, was enhanced. Moreover, the interaction between P2X7 and Fyn was identified by co-immunoprecipitation. After blocking the activity of Fyn or down-regulating the expression of Fyn, the migration of OPCs induced by BzATP was inhibited. These data indicate that P2X7 receptors/Fyn may mediate ATP-induced OPC migration under pathological conditions.
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References
Dawson MR, Levine JM, Reynolds R (2000) NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors? J Neurosci Res 61(5):471–479. doi:10.1002/1097-4547(20000901)61:5
Dawson MR, Polito A, Levine JM, Reynolds R (2003) NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS. Mol Cell Neurosci 24(2):476–488
Franklin RJ, Gilson JM, Blakemore WF (1997) Local recruitment of remyelinating cells in the repair of demyelination in the central nervous system. J Neurosci Res 50(2):337–344. doi:10.1002/(SICI)1097-4547(19971015)50:2
McTigue DM, Tripathi RB (2008) The life, death, and replacement of oligodendrocytes in the adult CNS. J Neurochem 107(1):1–19. doi:10.1111/j.1471-4159.2008.05570.x
Miller RH, Mi S (2007) Dissecting demyelination. Nat Neurosci 10(11):1351–1354
Franklin RJ, Ffrench-Constant C (2008) Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci 9(11):839–855. doi:10.1038/nrn2480
Tan AM, Zhang W, Levine JM (2005) NG2: a component of the glial scar that inhibits axon growth. J Anat 207(6):717–725. doi:10.1111/j.1469-7580.2005.00452.x
Sandvig A, Berry M, Barrett LB, Butt A, Logan A (2004) Myelin-, reactive glia-, and scar-derived CNS axon growth inhibitors: expression, receptor signaling, and correlation with axon regeneration. Glia 46(3):225–251. doi:10.1002/glia.10315
Levine JM, Reynolds R, Fawcett JW (2001) The oligodendrocyte precursor cell in health and disease. Trends Neurosci 24(1):39–47
North RA, Verkhratsky A (2006) Purinergic transmission in the central nervous system. Pflugers Arch 452(5):479–485. doi:10.1007/s00424-006-0060-y
Chen J, Shao C, Lu W, Yan C, Yao Q, Zhu M, Chen P, Gu P, Fu Y, Fan X (2014) Adenosine triphosphate-induced rabbit corneal endothelial cell Proliferation in vitro via the P2Y2-PI3K/Akt Signaling Axis. Cells Tissues Organs
Agresti C, Meomartini ME, Amadio S, Ambrosini E, Serafini B, Franchini L, Volonte C, Aloisi F, Visentin S (2005) Metabotropic P2 receptor activation regulates oligodendrocyte progenitor migration and development. Glia 50(2):132–144. doi:10.1002/glia.20160
D’Ambrosi N, Murra B, Cavaliere F, Amadio S, Bernardi G, Burnstock G, Volonte C (2001) Interaction between ATP and nerve growth factor signalling in the survival and neuritic outgrowth from PC12 cells. Neuroscience 108(3):527–534
Matute C, Torre I, Perez-Cerda F, Perez-Samartin A, Alberdi E, Etxebarria E, Arranz AM, Ravid R, Rodriguez-Antiguedad A, Sanchez-Gomez M, Domercq M (2007) P2X(7) receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis. J Neurosci 27(35):9525–9533
Franke H, Verkhratsky A, Burnstock G, Illes P (2012) Pathophysiology of astroglial purinergic signalling. Purinergic Signal 8(3):629–657. doi:10.1007/s11302-012-9300-0
Erb L, Liao Z, Seye CI, Weisman GA (2006) P2 receptors: intracellular signaling. Pflugers Arch 452(5):552–562. doi:10.1007/s00424-006-0069-2
Becker D, Woltersdorf R, Boldt W, Schmitz S, Braam U, Schmalzing G, Markwardt F (2008) The P2X7 carboxyl tail is a regulatory module of P2X7 receptor channel activity. J Biol Chem 283(37):25725–25734. doi:10.1074/jbc.M803855200
Surprenant A, Rassendren F, Kawashima E, North RA, Buell G (1996) The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272(5262):735–738
Costa-Junior HM, Sarmento Vieira F, Coutinho-Silva R (2011) C terminus of the P2X7 receptor: treasure hunting. Purinergic Signal 7(1):7–19. doi:10.1007/s11302-011-9215-1
Jiang LH, Baldwin JM, Roger S, Baldwin SA (2013) Insights into the molecular mechanisms underlying mammalian P2X7 receptor functions and contributions in diseases, revealed by structural modeling and single nucleotide polymorphisms. Front Pharmacol 4:55. doi:10.3389/fphar.2013.00055
Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H (2009) Purinergic signalling in the nervous system: an overview. Trends Neurosci 32(1):19–29. doi:10.1016/j.tins.2008.10.001
Khakh BS, Burnstock G (2009) The double life of ATP. Sci Am 301(6):84–90, 92
Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87(2):659–797
Sperlagh B, Vizi ES, Wirkner K, Illes P (2006) P2X7 receptors in the nervous system. Prog Neurobiol 78(6):327–346
Burnstock G, Krugel U, Abbracchio MP, Illes P (2011) Purinergic signalling: from normal behaviour to pathological brain function. Prog Neurobiol 95(2):229–274. doi:10.1016/j.pneurobio.2011.08.006
Muzzachi S, Blasi A, Ciani E, Favia M, Cardone RA, Marzulli D, Reshkin SJ, Merizzi G, Casavola V, Soleti A, Guerra L (2013) MED1101: a new dialdehydic compound regulating P2x7 receptor cell surface expression in U937 cells. Biol Cell 105(9):399–413. doi:10.1111/boc.201200088
Takai E, Tsukimoto M, Harada H, Kojima S (2014) Autocrine signaling via release of ATP and activation of P2X7 receptor influences motile activity of human lung cancer cells. Purinergic Signal 10(3):487–497. doi:10.1007/s11302-014-9411-x
Mayo C, Ren R, Rich C, Stepp MA, Trinkaus-Randall V (2008) Regulation by P2X7: epithelial migration and stromal organization in the cornea. Invest Ophthalmol Vis Sci 49(10):4384–4391. doi:10.1167/iovs.08-1688
Murphy N, Lynch MA (2012) Activation of the P2X(7) receptor induces migration of glial cells by inducing cathepsin B degradation of tissue inhibitor of metalloproteinase 1. J Neurochem 123(5):761–770. doi:10.1111/jnc.12031
Ghalali A, Wiklund F, Zheng H, Stenius U, Hogberg J (2014) Atorvastatin prevents ATP-driven invasiveness via P2X7 and EHBP1 signaling in PTEN-expressing prostate cancer cells. Carcinogenesis 35(7):1547–1555. doi:10.1093/carcin/bgu019
Liu X, Lu Y, Zhang Y, Li Y, Zhou J, Yuan Y, Gao X, Su Z, He C (2012) Slit2 regulates the dispersal of oligodendrocyte precursor cells via Fyn/RhoA signaling. J Biol Chem 287(21):17503–17516. doi:10.1074/jbc.M111.317610
Miyamoto Y, Yamauchi J, Tanoue A (2008) Cdk5 phosphorylation of WAVE2 regulates oligodendrocyte precursor cell migration through nonreceptor tyrosine kinase Fyn. J Neurosci 28(33):8326–8337. doi:10.1523/JNEUROSCI.1482-08.2008
Li C, Xiao L, Liu X, Yang W, Shen W, Hu C, Yang G, He C (2013) A functional role of NMDA receptor in regulating the differentiation of oligodendrocyte precursor cells and remyelination. Glia 61(5):732–749. doi:10.1002/glia.22469
Yang W, Xiao L, Li C, Liu X, Liu M, Shao Q, Wang D, Huang A, He C (2014) TIP30 inhibits oligodendrocyte precursor cell differentiation via cytoplasmic sequestration of Olig1. Glia. doi:10.1002/glia.22778
Bottenstein JE, Hunter SF, Seidel M (1988) CNS neuronal cell line-derived factors regulate gliogenesis in neonatal rat brain cultures. J Neurosci Res 20(3):291–303. doi:10.1002/jnr.490200303
Xiao L, Hu C, Yang W, Guo D, Li C, Shen W, Liu X, Aijun H, Dan W, He C (2013) NMDA receptor couples Rac1-GEF Tiam1 to direct oligodendrocyte precursor cell migration. Glia 61(12):2078–2099. doi:10.1002/glia.22578
Yamauchi J, Miyamoto Y, Torii T, Takashima S, Kondo K, Kawahara K, Nemoto N, Chan JR, Tsujimoto G, Tanoue A (2012) Phosphorylation of cytohesin-1 by Fyn is required for initiation of myelination and the extent of myelination during development. Sci Signal 5(243):ra69
Weissman TA, Riquelme PA, Ivic L, Flint AC, Kriegstein AR (2004) Calcium waves propagate through radial glial cells and modulate proliferation in the developing neocortex. Neuron 43(5):647–661. doi:10.1016/j.neuron.2004.08.015
Abbracchio MP, Saffrey MJ, Hopker V, Burnstock G (1994) Modulation of astroglial cell proliferation by analogues of adenosine and ATP in primary cultures of rat striatum. Neuroscience 59(1):67–76
Monif M, Reid CA, Powell KL, Smart ML, Williams DA (2009) The P2X7 receptor drives microglial activation and proliferation: a trophic role for P2X7R pore. J Neurosci 29(12):3781–3791. doi:10.1523/JNEUROSCI.5512-08.2009
Umemori H, Sato S, Yagi T, Aizawa S, Yamamoto T (1994) Initial events of myelination involve Fyn tyrosine kinase signalling. Nature 367(6463):572–576. doi:10.1038/367572a0
Colognato H, Ramachandrappa S, Olsen IM, Ffrench-Constant C (2004) Integrins direct Src family kinases to regulate distinct phases of oligodendrocyte development. J Cell Biol 167(2):365–375
Lu Z, Ku L, Chen Y, Feng Y (2005) Developmental abnormalities of myelin basic protein expression in fyn knock-out brain reveal a role of Fyn in posttranscriptional regulation. J Biol Chem 280(1):389–395
Kramer-Albers EM, White R (2011) From axon-glial signalling to myelination: the integrating role of oligodendroglial Fyn kinase. Cell Mol Life Sci 68(12):2003–2012. doi:10.1007/s00018-010-0616-z
Lin SC, Bergles DE (2004) Synaptic signaling between GABAergic interneurons and oligodendrocyte precursor cells in the hippocampus. Nat Neurosci 7(1):24–32. doi:10.1038/nn1162
Butt AM, Duncan A, Hornby MF, Kirvell SL, Hunter A, Levine JM, Berry M (1999) Cells expressing the NG2 antigen contact nodes of Ranvier in adult CNS white matter. Glia 26(1):84–91. doi:10.1002/(SICI)1098-1136(199903)26:1
Lin SC, Huck JH, Roberts JD, Macklin WB, Somogyi P, Bergles DE (2005) Climbing fiber innervation of NG2-expressing glia in the mammalian cerebellum. Neuron 46(5):773–785
Hughes EG, Kang SH, Fukaya M, Bergles DE (2013) Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain. Nat Neurosci 16(6):668–676. doi:10.1038/nn.3390
Coppi E, Maraula G, Fumagalli M, Failli P, Cellai L, Bonfanti E, Mazzoni L, Coppini R, Abbracchio MP, Pedata F, Pugliese AM (2013) UDP-glucose enhances outward K(+) currents necessary for cell differentiation and stimulates cell migration by activating the GPR17 receptor in oligodendrocyte precursors. Glia 61(7):1155–1171. doi:10.1002/glia.22506
Ceruti S, Vigano F, Boda E, Ferrario S, Magni G, Boccazzi M, Rosa P, Buffo A, Abbracchio MP (2011) Expression of the new P2Y-like receptor GPR17 during oligodendrocyte precursor cell maturation regulates sensitivity to ATP-induced death. Glia 59(3):363–378. doi:10.1002/glia.21107
Melani A, Turchi D, Vannucchi MG, Cipriani S, Gianfriddo M, Pedata F (2005) ATP extracellular concentrations are increased in the rat striatum during in vivo ischemia. Neurochem Int 47(6):442–448
North RA (2002) Molecular physiology of P2X receptors. Physiol Rev 82(4):1013–1067. doi:10.1152/physrev.00015.2002
Gribble FM, Loussouarn G, Tucker SJ, Zhao C, Nichols CG, Ashcroft FM (2000) A novel method for measurement of submembrane ATP concentration. J Biol Chem 275(39):30046–30049. doi:10.1074/jbc.M001010200
Fumagalli M, Daniele S, Lecca D, Lee PR, Parravicini C, Fields RD, Rosa P, Antonucci F, Verderio C, Trincavelli ML, Bramanti P, Martini C, Abbracchio MP (2011) Phenotypic changes, signaling pathway, and functional correlates of GPR17-expressing neural precursor cells during oligodendrocyte differentiation. J Biol Chem 286(12):10593–10604. doi:10.1074/jbc.M110.162867
Bianchi BR, Lynch KJ, Touma E, Niforatos W, Burgard EC, Alexander KM, Park HS, Yu H, Metzger R, Kowaluk E, Jarvis MF, van Biesen T (1999) Pharmacological characterization of recombinant human and rat P2X receptor subtypes. Eur J Pharmacol 376(1-2):127–138
Carrasquero LM, Delicado EG, Bustillo D, Gutierrez-Martin Y, Artalejo AR, Miras-Portugal MT (2009) P2X7 and P2Y13 purinergic receptors mediate intracellular calcium responses to BzATP in rat cerebellar astrocytes. J Neurochem 110(3):879–889. doi:10.1111/j.1471-4159.2009.06179.x
Iglesias R, Locovei S, Roque A, Alberto AP, Dahl G, Spray DC, Scemes E (2008) P2X7 receptor-Pannexin1 complex: pharmacology and signaling. Am J Physiol Cell Physiol 295(3):C752–760. doi:10.1152/ajpcell.00228.2008
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Ji-Feng Feng and Xiao-Fei Gao contributed equally to this work.
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Feng, JF., Gao, XF., Pu, Yy. et al. P2X7 receptors and Fyn kinase mediate ATP-induced oligodendrocyte progenitor cell migration. Purinergic Signalling 11, 361–369 (2015). https://doi.org/10.1007/s11302-015-9458-3
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DOI: https://doi.org/10.1007/s11302-015-9458-3