Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Transient Receptor Potential Cation Channel Subfamily M Member 2

  • Lin-Hua Jiang
  • Sharifah Alawieyah Syed Mortadza
Reference work entry
First Online:
DOI: https://doi.org/10.1007/978-3-319-67199-4_101875
How to cite

Synonyms

 Classical transient receptor potential 7;  Long transient receptor potential channel 2;  LTRPC2;  Melastatin-related transient receptor potential 2;  Transient receptor potential melastatin-related 2;  TRPC7;  TRPM2

Historical Background

Transient receptor potential (TRP) cation channel subfamily M member 2 (TRPM2) was identified in the search for mammalian genes encoding homologues of the transient receptor potential (Trp) proteins that forms Ca2+-permeable cationic channels required for photo-transduction in Drosophila melanogaster fruit fly (Hardie and Minke 1992). It was firstly named the seventh classical TRP protein (TRPC7) that exhibits sequence relatedness with Drosophila Trp proteins (Nagamine et al. 1998) and subsequently renamed LTRPC2, the second member of the long TRP channel protein family characterized with exceptionally long N- and C-termini (Harteneck et al. 2000). In the efforts devoted to unifying the terminology, the mammalian TRP proteins, 28 in total,...

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Notes

Acknowledgments

SSM is a recipient of Malaysian governmental scholarship. The researches in LHJ's lab described here have been supported by Wellcome Trust, Alzheimer’s Research Trust, Nature Science Foundation of China, Department of Education Henan Province, and Xinxiang Medical University. We apologize that we have not cited the literature in full due to space limitation.

References

  1. Alim I, Teves L, Li RW, Mori Y, Tymianski M. Modulation of NMDAR Subunit Expression by TRPM2 Channels Regulates Neuronal Vulnerability to Ischemic Cell Death. J Neurosci. 2013;33:17264–77.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Clapham DE. TRP channels as cellular sensors. Nature. 2003;426:517–24.CrossRefGoogle Scholar
  3. Di AK, Gao XP, Qian F, Kawamura T, Han J, Hecquet C, Ye RD, Vogel SM, Malik AB. The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation. Nat Immunol. 2012;13:29–34.CrossRefGoogle Scholar
  4. Du JY, Xie J, Yue LX. Intracellular calcium activates TRPM2 and its alternative spliced isoforms. Proc Natl Acad Sci U S A. 2009;106:7239–44.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Gao GF, Wang WW, Tadagavadi RK, Briley NE, Love MI, Miller BA, Reeves WB. TRPM2 mediates ischemic kidney injury and oxidant stress through RAC1. J Clin Invest. 2014;124:4989–5001.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Gelderblom M, Melzer N, Schattling B, Gob E, Hicking G, Arunachalam P, Bittner S, Ufer F, Herrmann AM, Bernreuther C, Glatzel M, Gerloff C, Kleinschnitz C, Meuth SG, Friese MA, Magnus T. Transient Receptor Potential Melastatin Subfamily Member 2 Cation Channel Regulates Detrimental Immune Cell Invasion in Ischemic Stroke. Stroke. 2014;45:3395–402.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T, Yamada H, Shimizu S, Mori E, Kudoh J, Shimizu N, Kurose H, Okada Y, Imoto K, Mori Y. LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell. 2002;9:163–73.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Haraguchi K, Kawamoto A, Isami K, Maeda S, Kusano A, Asakura K, Shirakawa H, Mori Y, Nakagawa T, Kaneko S. TRPM2 Contributes to inflammatory and neuropathic pain through the aggravation of pronociceptive inflammatory responses in mice. J Neurosci. 2012;32:3931–41.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Hardie RC, Minke B. The trp gene is essential for a light-activated Ca2+ channel in Drosophil photoreceptors. Neuron. 1992;8:643–51.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Harteneck C, Plant TD, Schultz G. From worm to man: three subfamilies of TRP channels. Trends Neurosci. 2000;23:159–66.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Hecquet CM, Ahmmed GU, Vogel SM, Malik AB. Role of TRPM2 channel in mediating H2O2-induced Ca2+ entry and endothelial hyperpermeability. Circ Res. 2008;102:347–55.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Hoffman NE, Miller BA, Wang JF, Elrod JW, Rajan S, Gao E, Song JL, Zhang XQ, Hirschler-Laszkiewicz I, Shanmughapriya S, Koch WJ, Feldman AM, Madesh M, Cheung JY. Ca2+ entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance. Am J Physiol Heart Circ Physiol. 2015;308:H637–H50.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Iordanov I, Mihalyi C, Toth B, Csanady L. The proposed channel-enzyme transient receptor potential melastatin 2 does not possess ADP ribose hydrolase activity. Elife. 2016;5:e17600.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Jiang LH, Yang W, Zou J, Beech DJ. TRPM2 channel properties, functions and therapeutic potentials. Expert Opin Ther Targets. 2010;14:973–88.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Kashio M, Sokabe T, Shintaku K, Uematsu T, Fukuta N, Kobayashi N, Mori Y, Tominaga M. Redox signal-mediated sensitization of transient receptor potential melastatin 2 (TRPM2) to temperature affects macrophage functions. Proc Natl Acad Sci U S A. 2012;109:6745–50.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Kheradpezhouh E, Ma LL, Morphett A, Barritt GJ, Rychkov GY. TRPM2 channels mediate acetaminophen-induced liver damage. Proc Natl Acad Sci U S A. 2014;111:3176–81.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Kheradpezhouh E, Barritt GJ, Rychkov GY. Curcumin inhibits activation of TRPM2 channels in rat hepatocytes. Redox Biol. 2016;7:1–7.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Knowles H, Heizer JW, Li Y, Chapman K, Ogden CA, Andreasen K, Shapland E, Kucera G, Mogan J, Humann J, Lenz LL, Morrison AD, Perraud AL. Transient Receptor Potential Melastatin 2 (TRPM2) ion channel is required for innate immunity against Listeria monocytogene. Proc Natl Acad Sci U S A. 2011;108:11578–83.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Kuhn FJP, Kuhn C, Luckhoff A. Functional characterisation of a TRPM2 orthologue from the sea anemone Nematostella vectensis in human cells. Sci Rep. 2015;5:8032.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Liao MF, Cao EH, Julius D, Cheng YF. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature. 2013;504:107–12.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Manna PT, Munsey TS, Abuarab N, Li FF, Asipu A, Howell G, Sedo A, Yang W, Naylor J, Beech DJ, Jiang LH, Sivaprasadarao A. TRPM2-mediated intracellular Zn2+ release triggers pancreatic beta-cell death. Biochem J. 2015;466:537–46.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Mei ZZ, Xia R, Beech DJ, Jiang LH. Intracellular coiled-coil domain engaged in subunit interaction and assembly of melastatin-related transient receptor potential channel 2. J Biol Chem. 2006;281:38748–56.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Montell C, Birnbaumer L, Flockerzi V, Bindels RJ, Brudorf EA, Caterina MJ, Clapham DE, Harteneck C, Heller S, Julius D, Kojima I, Mori Y, Penner R, Prawitt D, Scharenberg AM, Schultz G, Shimizu N, Zhu MX. A unified nomenclature for the superfamily of TRP cation channels. Mol Cell. 2002;9:229–31.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Moreau C, Kirchberger T, Swarbrick JM, Bartlett SJ, Fliegert R, Yorgan T, Bauche A, Harneit A, Guse AH, Potter BVL. Structure-activity relationship of Adenosine 5′-diphosphoribose at the transient receptor potential Melastatin 2 (TRPM2) channel: rational design of antagonists. J Med Chem. 2013;56:10079–102.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Nagamine K, Kudoh J, Minoshima S, Kawasaki K, Asakawa S, Ito F, Shimizu N. Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain. Genomics. 1998;54:124–31.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Nakayama S, Vest R, Traystman RJ, Herson PS. Sexually Dimorphic Response of TRPM2 Inhibition Following Cardiac Arrest-Induced Global Cerebral Ischemia in Mice. J Mol Neurosci. 2013;51:92–8.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Ostapchenko VG, Chen MA, Guzman MS, Xie YF, Lavine N, Fan J, Beraldo FH, Martyn AC, Belrose JC, Mori Y, MacDonald JF, Prado VF, Prado MAM, Jackson MF. The transient receptor potential melastatin 2 (TRPM2) channel contributes to beta-amyloid oligomer-related Neurotoxicity and memory impairment. J Neurosci. 2015;35:15157–69.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Park L, Wang G, Moore J, Girouard H, Zhou P, Anrather J, Iadecola C. The key role of transient receptor potential melastatin-2 channels in amyloid-beta-induced neurovascular dysfunction. Nat Commun. 2014;5:5318.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Perraud AL, Fleig A, Dunn CA, Bagley LA, Launay P, Schmitz C, Stokes AJ, Zhu QQ, Bessman MJ, Penner R, Kinet JP, Scharenberg AM. ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature. 2001;411:595–9.CrossRefGoogle Scholar
  30. Perraud AL, Takanishi CL, Shen B, Kang S, Smith MK, Schmitz C, Knowles HM, Ferraris D, Li WX, Zhang J, Stoddard BL, Scharenberg AM. Accumulation of free ADP-ribose from mitochondria mediates oxidative stress-induced gating of TRPM2 cation channels. J Biol Chem. 2005;280:6138–48.CrossRefGoogle Scholar
  31. Qian XW, Numata T, Zhang K, Li CX, Hou JC, Mori Y, Fang XM. Transient receptor potential melastatin 2 protects mice against polymicrobial sepsis by enhancing bacterial clearance. Anesthesiology. 2014;121:336–51.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Shimizu T, Macey TA, Quillinan N, Klawitter J, Perraud ALL, Traystman RJ, Herson PS. Androgen and PARP-1 regulation of TRPM2 channels after ischemic injury. J Cereb Blood Flow Metab. 2013;33:1549–55.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Song K, Wang H, Kamm GB, Pohle J, Reis FD, Heppenstall P, Wende H, Siemens J. The TRPM2 channel is a hypothalamic heat sensor that limits fever and can drive hypothermia. Science. 2016;353:1393–8.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Tan CH, McNaughton PA. The TRPM2 ion channel is required for sensitivity to warmth. Nature. 2016;536:460–3.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Toth B, Csanady L. Identification of Direct and Indirect Effectors of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel. J Biol Chem. 2010;285:30091–102.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Uchida K, Dezaki K, Damdindorj B, Inada H, Shiuchi T, Mori Y, Yada T, Minokoshi Y, Tominaga M. Lack of TRPM2 impaired insulin secretion and glucose metabolisms in mice. Diabetes. 2011;60:119–26.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Wehrhahn J, Kraft R, Harteneck C, Hauschildt S. Transient receptor potential melastatin 2 is required for lipopolysaccharide-induced cytokine production in human monocytes. J Immunol. 2010;184:2386–93.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Xia R, Mei ZZ, Mao HJ, Yang W, Dong L, Bradley H, Beech DJ, Jiang LH. Identification of pore residues engaged in determining divalent cationic permeation in transient receptor potential melastatin subtype channel. J Biol Chem. 2008;283:27426–32.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y, Negoro T, Hiroi T, Kiuchi Y, Okada T, Kaneko S, Lange I, Fleig A, Penner R, Nishi M, Takeshima H, Mori Y. TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med. 2008;14:738–47.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Yang KT, Chang WL, Yang PC, Chien CL, Lai MS, Su MJ, Wu ML. Activation of the transient receptor potential M2 channel and poly(ADP-ribose) polymerase is involved in oxidative stress-induced cardiomyocyte death. Cell Death Differ. 2006;13:1815–26.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Ye M, Yang W, Ainscough JF, Hu XP, Li X, Sedo A, Zhang XH, Zhang X, Chen Z, Li XM, Beech DJ, Sivaprasadarao A, Luo JH, Jiang LH. TRPM2 channel deficiency prevents delayed cytosolic Zn2+ accumulation and CA1 pyramidal neuronal death after transient global ischemia. Cell Death Dis. 2014;5:e1541.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Zhang ZY, Zhang WY, Jung DY, Ko HJ, Lee Y, Friedline RH, Lee E, Jun J, Ma ZX, Kim F, Tsitsilianos N, Chapman K, Morrison A, Cooper MP, Miller BA, Kim JK. TRPM2 Ca2+ channel regulates energy balance and glucose metabolism. Am J Physiol Endocrinol Metab. 2012;302:E807–16.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Zhong Z, Zhai Y, Liang S, Mori Y, Han R, Sutterwala FS, Qiao L. TPM2 links oxidative stress to NLRP3 inflammasome activation. Nat Commun. 2013;4:1611.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Zou J, Ainscough JF, Yang W, Sedo A, Yu SP, Mei ZZ, Sivaprasadarao A, Beech DJ, Jiang LH. A differential role of macrophage TRPM2 channels in Ca2+ signaling and cell death in early responses to H2O2. Am J Physiol Cell Physiol. 2013;305:C61–C9.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Lin-Hua Jiang
    • 1
    • 2
  • Sharifah Alawieyah Syed Mortadza
    • 1
  1. 1.School of Biomedical SciencesUniversity of LeedsLeedsUK
  2. 2.Department of Physiology and Neurobiology, and Sino-UK Joint Laboratory of Brain Function and InjuryXinxiang Medical UniversityXinxiangChina