TRPM1 Membrane Protein Introduction

Introduction of TRPM1

Transient receptor potential cation channel subfamily M member 1 (TRPM1), encoded by human TRPM1 gene, is a member of the melastatin-related transient receptor (TRPM) channel family. It has a biased expression in skin, especially melanocytes, and in testis. Specific mutations in the TRPM1 gene are thought to underlie autosomal recessive complete congenital stationary night blindness in humans. There are seven transcript variants produced by alternative splicing: isoform 1 ~ isoform 7, among which isoform 1 is chosen as the canonical sequence. The structure of TRPM1 contains an intracellular N and C termini, 6 transmembrane segments (S1-S6), and a pore region between S5 and S6. The N-terminal domain has a conserved region, and the C-terminal domain contains a TRP motif and a coiled-coil region.

Function of TRPM1 Membrane Protein

TRPM1 is a non-selective cation channel required for the depolarizing photoresponse of retinal ON bipolar cells. Fig.1 shows a model for TRPM1 gated by both the α and the βγ subunits of the G-protein Go. It can also function as a plasma membrane channel permeable to calcium. Reference to other orthologs, it is extrapolated that a microRNA located in an intron of the TRPM1 gene has a role in the suppression of melanoma metastasis. TRPM1 also participates in the synthesis of melanin. As a part of the metabotropic glutamate receptor 6 (mGluR6) signaling cascade, TRPM1 is reported to be involved in multiple other biological processes. It is reported that the TRPM1 gene expression is mediated by the class E basic helix-loop-helix protein 32, which is encoded by the MITF gene. A small molecular, hexamethylene bisacetamide (HBMA), is found to be able to up-regulate the expression of TRPM1.

Fig.1 The TRPM1 channel in ON-bipolar cells. (Ying, 2016)

Application of TRPM1 Membrane Protein in Literature

1. Ying X., et al. The TRPM1 channel in ON-bipolar cells is gated by both the α and the βγ subunits of the G-protein Go. Sci Rep. 2016, 6:20940. PubMed ID: 26883481
   
   

   This article demonstrates that both Gβγ and Gαo bind TRPM1 channels and cooperate to close them by co-immunoprecipitation and bioluminescent energy transfer assays.

2. Agosto M.A., et al. A Large Endoplasmic Reticulum-Resident Pool of TRPM1 in Retinal ON-Bipolar Cells. eNeuro. 2018, 5(3). PubMed ID: 30027108
   
   

   This article indicates that most of TRPM1 are located in the endoplasmic reticulum, from which it can potentially be transported to the dendritic tips as needed for ON light responses.

3. Takeuchi H., et al. Different Activity Patterns in Retinal Ganglion Cells of TRPM1 and mGluR6 Knockout Mice. Biomed Res Int. 2018. PubMed ID: 29854741
   
   

   This article demonstrates that a lack of TRPM1 in rod ON bipolar cells may have an effect on the maturation of synaptic terminal, but the lack of mGluR6 doesn’t have the same effect, suggesting that they are different in their effects on the postsynaptic circuitry and bipolar cell terminal.

4. Miraldi Utz V., et al. Presentation of TRPM1-Associated Congenital Stationary Night Blindness in Children. JAMA Ophthalmol. 2018, 136(4):389-398. PubMed ID: 29522070
   
   

   This report suggests that TRPM1-associated complete congenital stationary night blindness is a channelopathy that may present without complaints of night blindness in childhood.

5. Kozuka T., et al. The TRPM1 Channel Is Required for Development of the Rod ON Bipolar Cell-AII Amacrine Cell Pathway in the Retinal Circuit. J Neurosci. 2017, 37(41):9889-9900. PubMed ID: 28899920
   
   

   This article reveals that the development of rod bipolar cells and their synaptic formation with subsequent neurons requires TRPM1 transduction channel, which is independent of glutamate transmission.

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Reference

1. Ying X, et al. (2016). The TRPM1 channel in ON-bipolar cells is gated by both the α and the βγ subunits of the G-protein Go. Sci Rep. 6:20940.

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