|Transient receptor potential cation channel, subfamily M, member 2|
|External IDs||IUPHAR: ChEMBL: GeneCards:|
The TRPM2 gene is highly expressed in the brain and was implicated by both genetic linkage studies in families and then by case control or trio allelic association studies in the genetic aetiology of bipolar affective disorder (Manic Depression).
The physiological role of TRPM2 is not well understood. It was shown to be involved in insulin secretion. In the immune cells it mediates parts of the responses to TNF-alpha. A role has been suggested for TRPM2 in activation of NLRP3 inflammasome, the dysregulation of which is strongly associated with a number of auto inflammatory and metabolic diseases, such as gout, obesity and diabetes. In the brain it is involved in the toxicity of amyloid beta, a protein associated with Alzheimer's disease.
The protein encoded by this gene is a non-selective calcium-permeable cation channel and is part of the Transient Receptor Potential ion channel super family. The closest relative is the cold and menthol activated TRPM8 ion channel. While TRPM2 is not cold sensitive it is activated by heat. The TRPM2 ion channel is activated by free intracellular ADP-ribose in synergy with free intracellular calcium. ADP-Ribose is produced to by the enzyme PARP in response to oxidative stress and confers susceptibility to cell death. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.
- Gurling H (1998). "Chromosome 21 workshop". Psychiatr. Genet. 8 (2): 109–114. doi:10.1097/00041444-199800820-00015. PMID 9686433.
- McQuillin A, Bass NJ, Kalsi G, Lawrence J, Puri V, Choudhury K, Detera-Wadleigh SD, Curtis D, Gurling HM (February 2006). "Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3". Mol. Psychiatry 11 (2): 134–142. doi:10.1038/sj.mp.4001759. PMID 16205735.
- Xu C, Macciardi F, Li PP, Yoon IS, Cooke RG, Hughes B, Parikh SV, McIntyre RS, Kennedy JL, Warsh JJ (January 2006). "Association of the putative susceptibility gene, transient receptor potential protein melastatin type 2, with bipolar disorder". Am. J. Med. Genet. B Neuropsychiatr. Genet. 141B (1): 36–43. doi:10.1002/ajmg.b.30239. PMID 16252251.
- Togashi K, Hara Y, Tominaga T et al. (May 2006). "TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin secretion". EMBO J. 25 (9): 1804–1815. doi:10.1038/sj.emboj.7601083. PMC 1456947. PMID 16601673.
- 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 (July 2008). "TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration". Nat. Med. 14 (7): 738–47. doi:10.1038/nm1758. PMC 2789807. PMID 18542050.
- Zhong Z, Zhai Y, Liang S, Mori Y, Han R, Sutterwala FS, Qiao L (2013). "TRPM2 links oxidative stress to NLRP3 inflammasome activation". Nat Commun 4: 1611. doi:10.1038/ncomms2608. PMC 3605705. PMID 23511475.
- Miller BA (January 2006). "The role of TRP channels in oxidative stress-induced cell death". J. Membr. Biol. 209 (1): 31–41. doi:10.1007/s00232-005-0839-3. PMID 16685599.
- Csanády L, Törocsik B (February 2009). "Four Ca2+ ions activate TRPM2 channels by binding in deep crevices near the pore but intracellularly of the gate". J. Gen. Physiol. 133 (2): 189–203. doi:10.1085/jgp.200810109. PMC 2638199. PMID 19171771.
- "Entrez Gene: TRPM2 transient receptor potential cation channel, subfamily M, member 2".
- Clapham DE, Julius D, Montell C, Schultz G (2006). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacol. Rev. 57 (4): 427–450. doi:10.1124/pr.57.4.6. PMID 16382100.
- Eisfeld J, Lückhoff A (2007). "TRPM2". Handb Exp Pharmacol. Handbook of Experimental Pharmacology 179 (179): 237–252. doi:10.1007/978-3-540-34891-7_14. ISBN 978-3-540-34889-4. PMID 17217061.