TRPM

TRPM is a family of transient receptor potential ion channels (M standing for wikt:melastatin).[1] Functional TRPM channels are believed to form tetramers.[2] The TRPM family consists of eight different channels, TRPM1–TRPM8.[3]

Unlike the TRPC and TRPV sub-families, TRPM subunits do not contain N-terminal ankyrin repeat motifs but, rather, contain entire functional proteins in their C-termini. TRPM6 and TRPM7, for example, contain functional α-kinase segments, which are a type of serine/threonine-specific protein kinase.

Permeability and activation

The relative permeability of calcium and magnesium varies widely among TRPM channels.

TRPM4 and TRPM5 are impermeable to calcium.
TRPM3, TRPM6 and TRPM7 are highly permeable to both calcium and magnesium.

The mechanism of activation also varies greatly among TRPM channels.

TRPM2 is activated by ADP-ribose adenosine 5'-diphosphoribose and functions as a sensor of redox status in cells.[4]
TRPM4 and TRPM5 are activated by intracellular calcium.
TRPM8 can be activated by low temperatures, menthol, eucalyptol and icilin.[5][6]

Functions

Among the functional responsibilities of the TRPM channels are:

regulation of calcium oscillations after T cell activation[7] and prevention of cardiac conduction disorders (TRPM4).[8]
modulation of insulin secretion and sensory transduction in taste cells (TRPM5).[9]
cold sensation (TRPM8).
heat sensation and inflammatory pain (TRPM3).[10]
regulation of magnesium reabsorption in the kidneys and absorption in the intestines (TRPM6).[11]
regulation of cell adhesion (TRPM7).[12]

Genes

TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8

References

Kraft R, Harteneck C (2005). "The mammalian melastatin-related transient receptor potential cation channels: an overview". Pflügers Arch. 451 (1): 204–211. doi:10.1007/s00424-005-1428-0. PMID 15895246. S2CID 22823024.
Jiang LH (2007). "Subunit interaction in channel assembly and functional regulation of transient receptor potential melastatin (TRPM) channels". Biochem Soc Trans. 35 (1): 86–8. doi:10.1042/BST0350086. PMID 17233608.
Boesmans W, Owsianik G, Tack J, Voets T, Vanden Berghe P (2011). "TRP channels in neurogastroenterology: opportunities for therapeutic intervention". British Journal of Pharmacology. 162 (1): 18–37. doi:10.1111/j.1476-5381.2010.01009.x. PMC 3012403. PMID 20804496.
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 (2002). "LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death". Mol Cell. 9 (1): 163–173. doi:10.1016/S1097-2765(01)00438-5. PMID 11804595.
Behrendt HJ, Germann T, Gillen C, Hatt H, Jostock R (2004). "Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay". Br. J. Pharmacol. 141 (4): 737–745. doi:10.1038/sj.bjp.0705652. PMC 1574235. PMID 14757700.
Nilius B, Owsianik G, Voets T, Peters JA (2007). "Transient receptor potential cation channels in disease" (PDF). Physiol. Rev. 87 (1): 165–217. doi:10.1152/physrev.00021.2006. PMID 17237345.
Launay P, Cheng H, Srivatsan S, Penner R, Fleig A, Kinet J-P (2004). "TRPM4 regulates calcium oscillations after T cell activation". Science. 306 (5700): 1374–1377. doi:10.1126/science.1098845. PMID 15550671. S2CID 16459097.
Mathar, I; Jacobs, G; Kecskes, M; Menigoz, A; Philippaert, K; Vennekens, R (2014). TRPM4. Handbook of Experimental Pharmacology. Vol. 222. pp. 461–87. doi:10.1007/978-3-642-54215-2_18. ISBN 978-3-642-54214-5. PMID 24756717.
Philippaert, K; Pironet, A; Mesuere, M; Sones, W; Vermeiren, L; Kerselaers, S; Pinto, S; Segal, A; Antoine, N; Gysemans, C; Laureys, J; Lemaire, K; Gilon, P; Cuypers, E; Tytgat, J; Mathieu, C; Schuit, F; Rorsman, P; Talavera, K; Voets, T; Vennekens, R (31 March 2017). "Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity". Nature Communications. 8: 14733. doi:10.1038/ncomms14733. PMC 5380970. PMID 28361903.
Held, K; Voets, T; Vriens, J (2014). "TRPM3 in temperature sensing and beyond". Temperature (Austin, Tex.). 2 (2): 201–13. doi:10.4161/23328940.2014.988524. PMC 4844244. PMID 27227024.
Schlingmann KP, Weber S, Peters M, Niemann Nejsum L, Vitzthum H, Klingel K, Kratz M, Haddad E, Ristoff E, Dinour D, Syrrou M, Nielsen S, Sassen M, Waldegger S, Seyberth HW, Konrad M (2002). "Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family". Nat. Genet. 31 (2): 166–170. doi:10.1038/ng889. PMID 12032568. S2CID 40990544.
Su L-T, Agapito MA, Li M, Simonson WTN, Huttenlocher A, Habas R, Yue L, Runnels LW (2006). "TRPM7 regulates cell adhesion by controlling the calcium-dependent protease calpain". J. Biol. Chem. 281 (16): 11260–11270. doi:10.1074/jbc.M512885200. PMC 3225339. PMID 16436382.

External links

TRPM+Cation+Channels at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
"Transient Receptor Potential Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
"TRIP Database". a manually curated database of protein-protein interactions for mammalian TRP channels.

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[Kraft_2005-1] Kraft R, Harteneck C (2005). "The mammalian melastatin-related transient receptor potential cation channels: an overview". Pflügers Arch. 451 (1): 204–211. doi:10.1007/s00424-005-1428-0. PMID 15895246. S2CID 22823024.

[Jiang_2007-2] Jiang LH (2007). "Subunit interaction in channel assembly and functional regulation of transient receptor potential melastatin (TRPM) channels". Biochem Soc Trans. 35 (1): 86–8. doi:10.1042/BST0350086. PMID 17233608.

[Boesmans_2011-3] Boesmans W, Owsianik G, Tack J, Voets T, Vanden Berghe P (2011). "TRP channels in neurogastroenterology: opportunities for therapeutic intervention". British Journal of Pharmacology. 162 (1): 18–37. doi:10.1111/j.1476-5381.2010.01009.x. PMC 3012403. PMID 20804496.

[Hara_2002-4] 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 (2002). "LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death". Mol Cell. 9 (1): 163–173. doi:10.1016/S1097-2765(01)00438-5. PMID 11804595.

[Behrendt_2004-5] Behrendt HJ, Germann T, Gillen C, Hatt H, Jostock R (2004). "Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay". Br. J. Pharmacol. 141 (4): 737–745. doi:10.1038/sj.bjp.0705652. PMC 1574235. PMID 14757700.

[Nilius_2007-6] Nilius B, Owsianik G, Voets T, Peters JA (2007). "Transient receptor potential cation channels in disease" (PDF). Physiol. Rev. 87 (1): 165–217. doi:10.1152/physrev.00021.2006. PMID 17237345.

[7] Launay P, Cheng H, Srivatsan S, Penner R, Fleig A, Kinet J-P (2004). "TRPM4 regulates calcium oscillations after T cell activation". Science. 306 (5700): 1374–1377. doi:10.1126/science.1098845. PMID 15550671. S2CID 16459097.

[8] Mathar, I; Jacobs, G; Kecskes, M; Menigoz, A; Philippaert, K; Vennekens, R (2014). TRPM4. Handbook of Experimental Pharmacology. Vol. 222. pp. 461–87. doi:10.1007/978-3-642-54215-2_18. ISBN 978-3-642-54214-5. PMID 24756717.

[9] Philippaert, K; Pironet, A; Mesuere, M; Sones, W; Vermeiren, L; Kerselaers, S; Pinto, S; Segal, A; Antoine, N; Gysemans, C; Laureys, J; Lemaire, K; Gilon, P; Cuypers, E; Tytgat, J; Mathieu, C; Schuit, F; Rorsman, P; Talavera, K; Voets, T; Vennekens, R (31 March 2017). "Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity". Nature Communications. 8: 14733. doi:10.1038/ncomms14733. PMC 5380970. PMID 28361903.

[10] Held, K; Voets, T; Vriens, J (2014). "TRPM3 in temperature sensing and beyond". Temperature (Austin, Tex.). 2 (2): 201–13. doi:10.4161/23328940.2014.988524. PMC 4844244. PMID 27227024.

[Schlingmann_2002-11] Schlingmann KP, Weber S, Peters M, Niemann Nejsum L, Vitzthum H, Klingel K, Kratz M, Haddad E, Ristoff E, Dinour D, Syrrou M, Nielsen S, Sassen M, Waldegger S, Seyberth HW, Konrad M (2002). "Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family". Nat. Genet. 31 (2): 166–170. doi:10.1038/ng889. PMID 12032568. S2CID 40990544.

[12] Su L-T, Agapito MA, Li M, Simonson WTN, Huttenlocher A, Habas R, Yue L, Runnels LW (2006). "TRPM7 regulates cell adhesion by controlling the calcium-dependent protease calpain". J. Biol. Chem. 281 (16): 11260–11270. doi:10.1074/jbc.M512885200. PMC 3225339. PMID 16436382.