Transient receptor potential cation channel subfamily M member 4

Definition:

Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization. While it is activated by increase in intracellular Ca(2+), it is impermeable to it. Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway. Plays a role in keratinocyte differentiation.

References:

[1]. Bernd Nilius, et al. Decavanadate modulates gating of TRPM4 cation channels. J Physiol. 2004 Nov 1;560(Pt 3):753-65. [Content Brief]

[2]. Bernd Nilius, et al. The selectivity filter of the cation channel TRPM4. J Biol Chem. 2005 Jun 17;280(24):22899-906. [Content Brief]

[3]. Henrique Cheng, et al. TRPM4 controls insulin secretion in pancreatic beta-cells. Cell Calcium. 2007 Jan;41(1):51-61. [Content Brief]

[4]. Pierre Launay, et al. TRPM4 regulates calcium oscillations after T cell activation. Science. 2004 Nov 19;306(5700):1374-7. [Content Brief]

[5]. Paige A Winkler, et al. Electron cryo-microscopy structure of a human TRPM4 channel. Nature. 2017 Dec 14;552(7684):200-204. [Content Brief]

[6]. Bernd Nilius, et al. Voltage dependence of the Ca2+-activated cation channel TRPM4. J Biol Chem. 2003 Aug 15;278(33):30813-20. [Content Brief]

[7]. Bernd Nilius, et al. Regulation of the Ca2+ sensitivity of the nonselective cation channel TRPM4. J Biol Chem. 2005 Feb 25;280(8):6423-33. [Content Brief]

[8]. Zheng Zhang, et al. Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from desensitization. J Biol Chem. 2005 Nov 25;280(47):39185-92. [Content Brief]

[9]. Bernd Nilius, et al. The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate. EMBO J. 2006 Feb 8;25(3):467-78. [Content Brief]

[10]. Bernd Nilius, et al. Intracellular nucleotides and polyamines inhibit the Ca2+-activated cation channel TRPM4b. Pflugers Arch. 2004 Apr;448(1):70-5. [Content Brief]

[11]. Pierre Launay, et al. TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell. 2002 May 3;109(3):397-407. [Content Brief]

[12]. Ricardo Armisén, et al. TRPM4 enhances cell proliferation through up-regulation of the β-catenin signaling pathway. J Cell Physiol. 2011 Jan;226(1):103-9. [Content Brief]

[13]. Scott Earley, et al. Critical role for transient receptor potential channel TRPM4 in myogenic constriction of cerebral arteries. Circ Res. 2004 Oct 29;95(9):922-9. [Content Brief]

[14]. K Scott Weber, et al. Trpm4 differentially regulates Th1 and Th2 function by altering calcium signaling and NFAT localization. J Immunol. 2010 Sep 1;185(5):2836-46. [Content Brief]

[15]. X Z Xu, et al. Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10692-7. [Content Brief]

[16]. Huijun Wang, et al. Gain-of-Function Mutations in TRPM4 Activation Gate Cause Progressive Symmetric Erythrokeratodermia. J Invest Dermatol. 2019 May;139(5):1089-1097. [Content Brief]

[17]. Romain Guinamard, et al. Functional characterization of a Ca(2+)-activated non-selective cation channel in human atrial cardiomyocytes. J Physiol. 2004 Jul 1;558(Pt 1):75-83. [Content Brief]

[18]. Ryuichi Takezawa, et al. A pyrazole derivative potently inhibits lymphocyte Ca2+ influx and cytokine production by facilitating transient receptor potential melastatin 4 channel activity. Mol Pharmacol. 2006 Apr;69(4):1413-20. [Content Brief]

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