TRPM4 Membrane Protein Introduction

Introduction of TRPM4

Transient receptor potential cation channel subfamily M member 4 (TRPM4), also known as melastatin-4, PFHB1B, TRPM4B or LTrpC4, is a protein that in humans is encoded by the TRPM4 gene, which is located at the chromosome 19q13.33. TRPM4 shows a three-tiered architecture because of multiple transmembrane and cytosolic domains. It contains an N-terminal nucleotide-binding domain, which can bind ATP to inhibit channel activity; a C-terminal coiled-coil participating in the tetrameric assembly of the channel. TRPM4 has a wide expression in colon, prostate, small intestine, stomach, duodenum, skin, and multiple other tissues.

Function of TRPM4 Membrane Protein

TRPM4 is a calcium-activated, phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2)-modulated, non-selective cation channel
. Activation of TRPM4 can depolarize the plasma membrane through Na⁺ entry, which in turn enhances Ca²⁺ influx through Ca²⁺-permeable channels or otherwise modulates Ca²⁺ oscillations. It plays a role in myogenic constriction of cerebral arteries. Unlike many other TRP channels, TRPM4 is permeable to monovalent cations only. In pancreatic β-cells, it directly controls the secretion of insulin. TRPM4 can also affect cell motility of T-helper 1 (Th1) and T-helper 2 (Th2) and intervene in its cytokine production through the differential mediation of NFATC1 localization and calcium signaling. The expression of beta-catenin can be upregulated by TRPM4 and consequently lead to the enhancement of cell proliferation. In addition, TRPM4 is associated with cardiovascular disorders.

Fig.1 Cryo-EM structure of a human TRPM4 channel in complex with calcium and decavanadate. (Winkler, 2017)

Application of TRPM4 Membrane Protein in Literature

1. Kullmann F.A., et al. Involvement of TRPM4 in detrusor overactivity following spinal cord transection in mice. Naunyn Schmiedebergs Arch Pharmacol. 2018, 391(11):1191-1202. PubMed ID: 30054681
   
   

   This article demonstrates that TRPM4 channels are associated with overactivity of detrusor smooth muscle following spinal cord transection in mice, suggesting that repression of TRPM4 may be of benefit for improving it.

2. Bianchi B., et al. The ion channel TRPM4 in murine experimental autoimmune encephalomyelitis and in a model of glutamate-induced neuronal degeneration. Mol Brain. 2018, 11(1):41. PubMed ID: 29996905
   
   

   This article confirms that TRPM4 is important from early stages of murine experimental autoimmune encephalomyelitis, and suggests that use of these more efficient TRPM4 inhibitors could be novel protective therapeutic methods to treat glutamate-induced neurodegeneration.

3. Lee D.K., et al. PTPN6 regulates the cell-surface expression of TRPM4 channels in HEK293 cells. Pflugers Arch. 2018. PubMed ID: 29931651
   
   

   This article indicates that protein tyrosine phosphatase non-receptor type 6 (PTPN6)-dependent TRPM4 expression and its trafficking to the plasma membrane are crucial for cell proliferation in both HeLa cells and HEK293, suggesting that PTPN6 may be a novel therapeutic target for the treatment of pathologic diseases involving TRPM4.

4. Bianchi B., et al. Four TRPM4 Cation Channel Mutations Found in Cardiac Conduction Diseases Lead to Altered Protein Stability. Front Physiol. 2018, 9:177. PubMed ID: 29568272
   
   

   This report suggests that increased or decreased expression of several TRPM4 variants linked to ventricular arrhythmias or cardiac conduction disorders is found to be caused by the changed half-life of TRPM4 in contrast with the wild-type form.

5. Duan J., et al. Structure of full-length human TRPM4. Proc Natl Acad Sci U S A. 2018, 115(10):2377-2382. PubMed ID: 29463718
   
   

   This article determines human full-length TRPM4’s apo structure by cryo-EM with densities in its conduction pathway that is very likely to be Na⁺ ions.

TRPM4 Preparation Options

In order to provide high-quality membrane protein preparation service, we have developed a versatile Magic™ membrane protein production platform. Our experienced scientists will do their best to help you find a perfect match in your required formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-TRPM4 antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

Creative Biolabs has successfully produced, purified, stabilized and characterized many challenging membrane protein targets for global customers. We can provide membrane protein production service using a variety of strategies to meet the specific demands. If you are interested in the service we can provide, please feel free to contact us for more information.

Reference

1. Winkler P A, et al. (2017). Electron cryomicroscopy structure of a human TRPM4 channel. Nature. 552: 200-204.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.