Pannexin-1 hemichannel-mediated ATP release together with P2X1 and P2X4 receptors regulate T-cell activation at the immune synap
Authors:
Journal: Blood
Publication Type: Journal Article
Date: 2010
DOI: PMC2981474
ID: 20660288
Abstract
Engagement of T cells with antigen-presenting cells requires T-cell receptor (TCR) stimulation at the immune synapse. We previously reported that TCR stimulation induces the release of cellular adenosine-5'-triphosphate (ATP) that regulates T-cell activation. Here we tested the roles of pannexin-1 hemichannels, which have been implicated in ATP release, and of various P2X receptors, which serve as ATP-gated Ca(2+) channels, in events that control T-cell activation. TCR stimulation results in the translocation of P2X1 and P2X4 receptors and pannexin-1 hemichannels to the immune synapse, while P2X7 receptors remain uniformly distributed on the cell surface. Removal of extracellular ATP or inhibition, mutation, or silencing of P2X1 and P2X4 receptors inhibits Ca(2+) entry, nuclear factors of activated T cells (NFAT) activation, and induction of interleukin-2 synthesis. Inhibition of pannexin-1 hemichannels suppresses TCR-induced ATP release, Ca(2+) entry, and T-cell activation. We conclude that pannexin-1 hemichannels and P2X1 and P2X4 receptors facilitate ATP release and autocrine feedback mechanisms that control Ca(2+) entry and T-cell activation at the immune synapse.
Chemical List
- Calcium Channels|||Connexins|||Interleukin-2|||Membrane Proteins|||NFATC Transcription Factors|||Neoplasm Proteins|||Nerve Tissue Proteins|||ORAI1 Protein|||ORAI1 protein, human|||PANX1 protein, human|||Receptors, Purinergic P2X1|||Receptors, Purinergic P2X4|||Receptors, Purinergic P2X5|||Receptors, Purinergic P2X7|||STIM1 protein, human|||Stromal Interaction Molecule 1|||Adenosine Triphosphate|||Calcium
Reference List
- Feske S, Gwack Y, Prakriya M, et al. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature. 2006;441(7090):179–185.|||Park CY, Hoover PJ, Mullins FM, et al. STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell. 2009;136(5):876–890.|||Hogan PG, Lewis RS, Rao A. Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. Annu Rev Immunol. 2010;28:491–533.|||Lioudyno MI, Kozak JA, Penna A, et al. Orai1 and STIM1 move to the immunological synapse and are up-regulated during T cell activation. Proc Natl Acad Sci U S A. 2008;105(6):2011–2016.|||Oh-hora M, Rao A. Calcium signaling in lymphocytes. Curr Opin Immunol. 2008;20(3):250–258.|||Hogan PG, Chen L, Nardone J, Rao A. Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 2003;17(18):2205–2232.|||Gwack Y, Feske S, Srikanth S, Hogan PG, Rao A. Signalling to transcription: store-operated Ca2+ entry and NFAT activation in lymphocytes. Cell Calcium. 2007;42(2):145–156.|||Yip L, Woehrle T, Corriden R, et al. Autocrine regulation of T-cell activation by ATP release and P2X7 receptors. FASEB J. 2009;23(6):1685–1693.|||Filippini A, Taffs RE, Sitkovsky MV. Extracellular ATP in T-lymphocyte activation: possible role in effector functions. Proc Natl Acad Sci U S A. 1990;87(21):8267–8271.|||Schenk U, Westendorf AM, Radaelli E, et al. Purinergic control of T cell activation by ATP released through pannexin-1 hemichannels. Sci Signal. 2008;1(39):ra6.|||Dubyak GR. Purinergic signaling at immunological synapses. J Auton Nerv Syst. 2000;81(1–3):64–68.|||Chen Y, Corriden R, Inoue Y, et al. ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science. 2006;314(5806):1792–1795.|||Corriden R, Insel PA, Junger WG. A novel method using fluorescence microscopy for real-time assessment of ATP release from individual cells. Am J Physiol Cell Physiol. 2007;293(4):C1420–1425.|||Yip L, Cheung CW, Corriden R, Chen Y, Insel PA, Junger WG. Hypertonic stress regulates T-cell function by the opposing actions of extracellular adenosine triphosphate and adenosine. Shock. 2007;27(3):242–250.|||Loomis WH, Namiki S, Ostrom RS, Insel PA, Junger WG. Hypertonic stress increases T cell interleukin-2 expression through a mechanism that involves ATP release, P2 receptor, and p38 MAPK activation. J Biol Chem. 2003;278(7):4590–4596.|||Langston HP, Ke Y, Gewirtz AT, Dombrowski KE, Kapp JA. Secretion of IL-2 and IFN-gamma, but not IL-4, by antigen-specific T cells requires extracellular ATP. J Immunol. 2003;170(6):2962–2970.|||Vial C, Roberts JA, Evans RJ. Molecular properties of ATP-gated P2X receptor ion channels. Trends Pharmacol Sci. 2004;25(9):487–493.|||North RA. Molecular physiology of P2X receptors. Physiol Rev. 2002;82(4):1013–1067.|||Di Virgilio F, Chiozzi P, Ferrari D, et al. Nucleotide receptors: an emerging family of regulatory molecules in blood cells. Blood. 2001;97(3):587–600.|||Sluyter R, Barden JA, Wiley JS. Detection of P2X purinergic receptors on human B lymphocytes. Cell Tissue Res. 2001;304(2):231–236.|||Viola A, Contento RL, Molon B. Signaling amplification at the immunological synapse. Curr Top Microbiol Immunol. 340:109–122.|||Ennion SJ, Evans RJ. P2X(1) receptor subunit contribution to gating revealed by a dominant negative PKC mutant. Biochem Biophys Res Commun. 2002;291(3):611–616.|||Silberberg SD, Chang TH, Swartz KJ. Secondary structure and gating rearrangements of transmembrane segments in rat P2X4 receptor channels. J Gen Physiol. 2005;125(4):347–359.|||Charvet C, Canonigo AJ, Billadeau DD, Altman A. Membrane localization and function of Vav3 in T cells depend on its association with the adapter SLP-76. J Biol Chem. 2005;280(15):15289–15299.|||Bo X, Jiang LH, Wilson HL, et al. Pharmacological and biophysical properties of the human P2X5 receptor. Mol Pharmacol. 2003;63(6):1407–1416.|||Jarvis MF, Khakh BS. ATP-gated P2X cation-channels. Neuropharmacology. 2009;56(1):208–215.|||Zhang SL, Yu Y, Roos J, et al. STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature. 2005;437(7060):902–905.|||Prakriya M, Lewis RS. CRAC channels: activation, permeation, and the search for a molecular identity. Cell Calcium. 2003;33(5–6):311–321.|||Barr VA, Bernot KM, Srikanth S, et al. Dynamic movement of the calcium sensor STIM1 and the calcium channel Orai1 in activated T-cells: puncta and distal caps. Mol Biol Cell. 2008;19(7):2802–2817.|||Ikeda M. Characterization of functional P2X(1) receptors in mouse megakaryocytes. Thromb Res. 2007;119(3):343–353.|||Sim JA, Broomhead HE, North RA. Ectodomain lysines and suramin block of P2X1 receptors. J Biol Chem. 2008;283(44):29841–29846.|||Torres GE, Egan TM, Voigt MM. Hetero-oligomeric assembly of P2X receptor subunits. Specificities exist with regard to possible partners. J Biol Chem. 1999;274(10):6653–6659.|||Nicke A, Kerschensteiner D, Soto F. Biochemical and functional evidence for heteromeric assembly of P2X1 and P2X4 subunits. J Neurochem. 2005;92(4):925–933.|||Ma W, Hui H, Pelegrin P, Surprenant A. Pharmacological characterization of pannexin-1 currents expressed in mammalian cells. J Pharmacol Exp Ther. 2009;328(2):409–418.|||Yokosuka T, Saito T. Dynamic regulation of T-cell costimulation through TCR-CD28 microclusters. Immunol Rev. 2009;229(1):27–40.|||Randriamampita C, Trautmann A. Ca2+ signals and T lymphocytes; “New mechanisms and functions in Ca2+ signalling”. Biol Cell. 2004;96(1):69–78.|||Zeyda M, Stulnig TM. Lipid Rafts & Co.: an integrated model of membrane organization in T cell activation. Prog Lipid Res. 2006;45(3):187–202.|||Davis DM, Dustin ML. What is the importance of the immunological synapse? Trends Immunol. 2004;25(6):323–327.|||Vial C, Fung CY, Goodall AH, Mahaut-Smith MP, Evans RJ. Differential sensitivity of human platelet P2X1 and P2Y1 receptors to disruption of lipid rafts. Biochem Biophys Res Commun. 2006;343(2):415–419.|||Vial C, Evans RJ. Disruption of lipid rafts inhibits P2X1 receptor-mediated currents and arterial vasoconstriction. J Biol Chem. 2005;280(35):30705–30711.|||Barth K, Weinhold K, Guenther A, Linge A, Gereke M, Kasper M. Characterization of the molecular interaction between caveolin-1 and the P2X receptors 4 and 7 in E10 mouse lung alveolar epithelial cells. Int J Biochem Cell Biol. 2008;40(10):2230–2239.|||Yeromin AV, Zhang SL, Jiang W, Yu Y, Safrina O, Cahalan MD. Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai. Nature. 2006;443(7108):226–229.|||Oh-hora M. Calcium signaling in the development and function of T-lineage cells. Immunol Rev. 2009;231(1):210–224.|||Vig M, Peinelt C, Beck A, et al. CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science. 2006;312(5777):1220–1223.|||Wang Y, Deng X, Zhou Y, et al. STIM protein coupling in the activation of Orai channels. Proc Natl Acad Sci U S A. 2009;106(18):7391–7396.|||Ambudkar IS, Ong HL, Liu X, Bandyopadhyay BC, Cheng KT. TRPC1: the link between functionally distinct store-operated calcium channels. Cell Calcium. 2007;42(2):213–223.|||Guo C, Masin M, Qureshi OS, Murrell-Lagnado RD. Evidence for functional P2X4/P2X7 heteromeric receptors. Mol Pharmacol. 2007;72(6):1447–1456.|||Dubyak GR. Go it alone no more—P2X7 joins the society of heteromeric ATP-gated receptor channels. Mol Pharmacol. 2007;72(6):1402–1405.|||Casas-Pruneda G, Reyes JP, Perez-Flores G, Perez-Cornejo P, Arreola J. Functional interactions between P2X4 and P2X7 receptors from mouse salivary epithelia. J Physiol. 2009;587(Pt 12):2887–2901.