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TRPM2

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Template:PBB Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a protein that in humans is encoded by the TRPM2 gene.

Function

The TRPM2 gene is highly expressed in the brain and was implicated by both genetic linkage studies in families[1] and then by case control or trio allelic association studies in the genetic aetiology of bipolar affective disorder (Manic Depression).[2][3] The physiological role of TRPM2 is not well understood. It was shown to be involved in insulin secretion.[4] In the immune cells it mediates parts of the responses to TNF-alpha.[5] In the brain it is involved in the toxicity of amyloid beta, a protein associated with Alzheimer's disease.[6]

Structure

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.[4] The TRPM2 ion channel is activated by free intracellular ADP-ribose in synergy with free intracellular calcium.[7] 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.[8]

See also

References

  1. ^ Gurling H (1998). "Chromosome 21 workshop". Psychiatr. Genet. 8 (2): 109–13. doi:10.1097/00041444-199800820-00015. PMID 9686433.
  2. ^ McQuillin A, Bass NJ, Kalsi G, Lawrence J, Puri V, Choudhury K, Detera-Wadleigh SD, Curtis D, Gurling HM (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): 134–42. doi:10.1038/sj.mp.4001759. PMID 16205735. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ Xu C, Macciardi F, Li PP, Yoon IS, Cooke RG, Hughes B, Parikh SV, McIntyre RS, Kennedy JL, Warsh JJ (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ a b Togashi K, Hara Y, Tominaga T; et al. (2006). "TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin secretion". EMBO J. 25 (9): 1804–15. doi:10.1038/sj.emboj.7601083. PMC 1456947. PMID 16601673. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Yamamoto S, Shimizu S, Kiyonaka S; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Miller BA (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  7. ^ Csanády L, Törocsik B (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  8. ^ "Entrez Gene: TRPM2 transient receptor potential cation channel, subfamily M, member 2".

Further reading

  • Shahidul, Islam (2011). Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. Vol. 704. Berlin: Springer. p. 700. ISBN 978-94-007-0264-6. {{cite book}}: Unknown parameter |month= ignored (help)
  • 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): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Eisfeld J, Lückhoff A (2007). "TRPM2". Handb Exp Pharmacol. 179 (179): 237–52. doi:10.1007/978-3-540-34891-7_14. PMID 17217061.
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