TRPM2: a Multifunctional Ion Channel for Calcium Signalling

Overview

Journal J Physiol

Specialty Physiology

Date 2010 Dec 8

PMID 21135052

Citations 139

Authors

Adriana Sumoza-Toledo

Reinhold Penner

Affiliations

Soon will be listed here.

Abstract

The transient potential receptor melastatin-2 (TRPM2) channel has emerged as an important Ca(2+) signalling mechanism in a variety of cells, contributing to cellular functions that include cytokine production, insulin release, cell motility and cell death. Its ability to respond to reactive oxygen species has made TRPM2 a potential therapeutic target for chronic inflammation, neurodegenerative diseases, and oxidative stress-related pathologies. TRPM2 is a non-selective, calcium (Ca(2+))-permeable cation channel of the melastatin-related transient receptor potential (TRPM) ion channel subfamily. It is activated by intracellular adenosine diphosphate ribose (ADPR) through a diphosphoribose hydrolase domain in its C-terminus and regulated through a variety of factors, including synergistic facilitation by [Ca(2+)](i), cyclic ADPR, H(2)O(2), NAADP, and negative feedback regulation by AMP and permeating protons (pH). In addition to its role mediating Ca(2+) influx into the cells, TRPM2 can also function as a lysosomal Ca(2+) release channel, contributing to cell death. The physiological and pathophysiological context of ROS-mediated events makes TRPM2 a promising target for the development of therapeutic tools of inflammatory and degenerative diseases.

Citing Articles

Thermo-TRP regulation by endogenous factors and its physiological function at core body temperature.

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Immunohistochemical investigation of transient receptor potential melastatin-2 and spexin immunoreactivity in atopic dermatitis and mycosis fungoides.

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[Construction of HEK293T cell line stably expressing TRPM2 channel based on PiggyBac transposition system and its application in drug screening for cerebral ischemia and other diseases].

Ying K, Hua N, Luo Y, Liu X, Liu M, Yang W Zhejiang Da Xue Xue Bao Yi Xue Ban. 2024; 53(5):604-614.

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References

Csanady L . Permeating proton found guilty in compromising TRPM2 channel activity. J Physiol. 2010; 588(Pt 10):1661-2. PMC: 2887984. DOI: 10.1113/jphysiol.2010.190223. View

Hecquet C, Ahmmed G, Vogel S, Malik A . Role of TRPM2 channel in mediating H2O2-induced Ca2+ entry and endothelial hyperpermeability. Circ Res. 2007; 102(3):347-55. DOI: 10.1161/CIRCRESAHA.107.160176. View

Hill K, Benham C, McNulty S, Randall A . Flufenamic acid is a pH-dependent antagonist of TRPM2 channels. Neuropharmacology. 2004; 47(3):450-60. DOI: 10.1016/j.neuropharm.2004.04.014. View

Bessman M, Frick D, OHandley S . The MutT proteins or "Nudix" hydrolases, a family of versatile, widely distributed, "housecleaning" enzymes. J Biol Chem. 1996; 271(41):25059-62. DOI: 10.1074/jbc.271.41.25059. View

Tong L, Denu J . Function and metabolism of sirtuin metabolite O-acetyl-ADP-ribose. Biochim Biophys Acta. 2010; 1804(8):1617-25. PMC: 3310390. DOI: 10.1016/j.bbapap.2010.02.007. View

Song M, Yuan J . Introduction to TRP channels: structure, function, and regulation. Adv Exp Med Biol. 2010; 661:99-108. DOI: 10.1007/978-1-60761-500-2_6. View

Togashi K, Inada H, Tominaga M . Inhibition of the transient receptor potential cation channel TRPM2 by 2-aminoethoxydiphenyl borate (2-APB). Br J Pharmacol. 2008; 153(6):1324-30. PMC: 2275460. DOI: 10.1038/sj.bjp.0707675. View

Togashi K, Hara Y, Tominaga T, Higashi T, Konishi Y, Mori Y . TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin secretion. EMBO J. 2006; 25(9):1804-15. PMC: 1456947. DOI: 10.1038/sj.emboj.7601083. View

Olah M, Jackson M, Li H, Perez Y, Sun H, Kiyonaka S . Ca2+-dependent induction of TRPM2 currents in hippocampal neurons. J Physiol. 2009; 587(Pt 5):965-79. PMC: 2673769. DOI: 10.1113/jphysiol.2008.162289. View

10.

Dong X, Wang X, Xu H . TRP channels of intracellular membranes. J Neurochem. 2010; 113(2):313-28. PMC: 2905631. DOI: 10.1111/j.1471-4159.2010.06626.x. View

11.

Yamamoto S, Takahashi N, Mori Y . Chemical physiology of oxidative stress-activated TRPM2 and TRPC5 channels. Prog Biophys Mol Biol. 2010; 103(1):18-27. DOI: 10.1016/j.pbiomolbio.2010.05.005. View

12.

Cheeseman K, Slater T . An introduction to free radical biochemistry. Br Med Bull. 1993; 49(3):481-93. DOI: 10.1093/oxfordjournals.bmb.a072625. View

13.

Gees M, Colsoul B, Nilius B . The role of transient receptor potential cation channels in Ca2+ signaling. Cold Spring Harb Perspect Biol. 2010; 2(10):a003962. PMC: 2944357. DOI: 10.1101/cshperspect.a003962. View

14.

Naziroglu M, Luckhoff A . A calcium influx pathway regulated separately by oxidative stress and ADP-Ribose in TRPM2 channels: single channel events. Neurochem Res. 2008; 33(7):1256-62. DOI: 10.1007/s11064-007-9577-5. View

15.

Hermosura M, Cui A, Go R, Davenport B, Shetler C, Heizer J . Altered functional properties of a TRPM2 variant in Guamanian ALS and PD. Proc Natl Acad Sci U S A. 2008; 105(46):18029-34. PMC: 2584682. DOI: 10.1073/pnas.0808218105. View

16.

Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y . TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med. 2008; 14(7):738-47. PMC: 2789807. DOI: 10.1038/nm1758. View

17.

Bari M, Akbar S, Eweida M, Kuhn F, Gustafsson A, Luckhoff A . H2O2-induced Ca2+ influx and its inhibition by N-(p-amylcinnamoyl) anthranilic acid in the beta-cells: involvement of TRPM2 channels. J Cell Mol Med. 2009; 13(9B):3260-7. PMC: 4516483. DOI: 10.1111/j.1582-4934.2009.00737.x. View

18.

Partida-Sanchez S, Iribarren P, Moreno-Garcia M, Gao J, Murphy P, Oppenheimer N . Chemotaxis and calcium responses of phagocytes to formyl peptide receptor ligands is differentially regulated by cyclic ADP ribose. J Immunol. 2004; 172(3):1896-906. DOI: 10.4049/jimmunol.172.3.1896. View

19.

Csanady L, Torocsik B . Four Ca2+ ions activate TRPM2 channels by binding in deep crevices near the pore but intracellularly of the gate. J Gen Physiol. 2009; 133(2):189-203. PMC: 2638199. DOI: 10.1085/jgp.200810109. View

20.

Romero J, Germer S, Castonguay A, Barton N, Martin M, Zee R . Gene variation of the transient receptor potential cation channel, subfamily M, member 2 (TRPM2) and type 2 diabetes mellitus: A case-control study. Clin Chim Acta. 2010; 411(19-20):1437-40. DOI: 10.1016/j.cca.2010.05.036. View