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TRPM1
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<h2 id="function">Function</h2> <p>The protein encoded by this gene is a member of the <a href="/facts/Transient_receptor_potential/bbJSljzL">transient receptor potential</a> (TRP) family of non-selective cation <a href="/facts/Ion_channel/A46LARFH">channels</a>. It is expressed in the retina, in a subset of <a href="/facts/Retina_bipolar_cell/aUWUNcnn">bipolar cells</a> termed ON bipolar cells.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a><a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> These cells form <a href="/facts/Synapse/vdMRJCUn">synapses</a> with either <a href="/facts/Rod_cell/mNd9Sf1E">rods</a> or <a href="/facts/Cone_cell/JoQeEzoF">cones</a>, collecting signals from them. In the dark, the signal arrives in the form of the <a href="/facts/Neurotransmitter/LlpYFSU3">neurotransmitter</a> glutamate, which is detected by a <a href="/facts/G_protein-coupled_receptor/0arUMkQc">G protein-coupled receptor</a> (GPCR) signal transduction cascade. Detection of glutamate by the GPCR <a href="/facts/Metabotropic_glutamate_receptor_6/LMDnekL5">Metabotropic glutamate receptor 6</a> results in closing of the TRPM1 channel. At the onset of light, glutamate release is halted and mGluR6 is deactivated; this results in opening of the TRPM1 channel, influx of sodium and calcium, and <a href="/facts/Depolarization/qGX8lFXE">depolarization</a> of the bipolar cell.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a><a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> </p><p>In addition to the retina, TRPM1 is also expressed in <a href="/facts/Melanocyte/z8KowoXP">melanocytes</a>, which are melanin-producing cells in the skin. The expression of TRPM1 is inversely correlated with <a href="/facts/Melanoma/qdT7E97Y">melanoma</a> aggressiveness, suggesting that it might suppress <a href="/facts/Melanoma/qdT7E97Y">melanoma</a> <a href="/facts/Metastasis/4dadbm6z">metastasis</a>.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> However, subsequent work showed that a <a href="/facts/MicroRNA/UjqbYYpe">microRNA</a> located in an <a href="/facts/Intron/LS6YdBEK">intron</a> of the <i>TRPM1</i> gene, rather than the TRPM1 protein itself, is responsible for the tumor suppressor function.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a><a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> The expression of both TRPM1 and the microRNA are regulated by the <a href="/facts/Microphthalmia-associated_transcription_factor/loE6X4HQ">Microphthalmia-associated transcription factor</a>.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a><a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> </p> <h2 id="clinical-significance">Clinical significance</h2> <p>Mutations in TRPM1 are associated with <a href="/facts/Congenital_stationary_night_blindness/JeS9U9Ta">congenital stationary night blindness</a> in humans <a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a><a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a><a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a><a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> and coat spotting patterns in <a href="/facts/Appaloosa/7kQfHv6f">Appaloosa</a> horses.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/TRPM/he77tVJj">TRPM</a></li></ul> <h2 id="external-links">External links</h2> <ul><li><a href="https://meshb.nlm.nih.gov/record/ui?name=TRPM1+protein%2C+human">TRPM1+protein,+human</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li></ul> <p><i>This article incorporates text from the <a href="/facts/United_States_National_Library_of_Medicine/Hzty0MCX">United States National Library of Medicine</a>, which is in the <a href="/facts/Public_domain/YWKMDKw4">public domain</a>.</i> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Hunter JJ, Shao J, Smutko JS, Dussault BJ, Nagle DL, Woolf EA, Holmgren LM, Moore KJ, Shyjan AW (Nov 1998). "Chromosomal localization and genomic characterization of the mouse melastatin gene (Mlsn1)". Genomics. 54 (1): 116–23. doi:10.1006/geno.1998.5549. PMID 9806836. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Duncan LM, Deeds J, Hunter J, Shao J, Holmgren LM, Woolf EA, Tepper RI, Shyjan AW (Apr 1998). "Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis". Cancer Research. 58 (7): 1515–20. PMID 9537257. <a href="/wiki/PMID_(identifier)" target="_blank">/wiki/PMID_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Clapham DE, Julius D, Montell C, Schultz G (Dec 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacological Reviews. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100. S2CID 17936350. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Morgans CW, Zhang J, Jeffrey BG, Nelson SM, Burke NS, Duvoisin RM, Brown RL (2009). "TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells". Proc Natl Acad Sci U S A. 106 (45): 19174–8. Bibcode:2009PNAS..10619174M. doi:10.1073/pnas.0908711106. PMC 2776419. PMID 19861548. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776419" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776419</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Koike C, Obara T, Uriu Y, Numata T, Sanuki R, Miyata K, Koyasu T, Ueno S, Funabiki K, Tani A, Ueda H, Kondo M, Mori Y, Tachibana M, Furukawa T (2010). "TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade". Proc Natl Acad Sci U S A. 107 (1): 332–7. Bibcode:2010PNAS..107..332K. doi:10.1073/pnas.0912730107. PMC 2806705. PMID 19966281. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806705" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806705</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Martemyanov KA, Sampath AP (2017). "The Transduction Cascade in Retinal ON-Bipolar Cells: Signal Processing and Disease". Annu Rev Vis Sci. 3: 25–51. doi:10.1146/annurev-vision-102016-061338. PMC 5778350. PMID 28715957. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778350" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778350</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Schneider FM, Mohr F, Behrendt M, Oberwinkler J (2015). "Properties and functions of TRPM1 channels in the dendritic tips of retinal ON-bipolar cells". Eur J Cell Biol. 94 (7–9): 420–7. doi:10.1016/j.ejcb.2015.06.005. PMID 26111660. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>"Entrez Gene: TRPM1 transient receptor potential cation channel, subfamily M, member 1". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4308" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4308</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Levy C, Khaled M, Iliopoulos D, Janas MM, Schubert S, Pinner S, Chen PH, Li S, Fletcher AL, Yokoyama S, Scott KL, Garraway LA, Song JS, Granter SR, Turley SJ, Fisher DE, Novina CD (2010). "Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma". Mol Cell. 40 (5): 841–9. doi:10.1016/j.molcel.2010.11.020. PMC 3004467. PMID 21109473. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004467" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004467</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Guo H, Carlson JA, Slominski A (2012). "Role of TRPM in melanocytes and melanoma". Exp Dermatol. 21 (9): 650–4. doi:10.1111/j.1600-0625.2012.01565.x. PMC 3422761. PMID 22897572. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422761" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422761</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Miller AJ, Du J, Rowan S, Hershey CL, Widlund HR, Fisher DE (Jan 2004). "Transcriptional regulation of the melanoma prognostic marker melastatin (TRPM1) by MITF in melanocytes and melanoma". Cancer Research. 64 (2): 509–16. doi:10.1158/0008-5472.CAN-03-2440. PMID 14744763. <a href="https://doi.org/10.1158%2F0008-5472.CAN-03-2440" target="_blank">https://doi.org/10.1158%2F0008-5472.CAN-03-2440</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. <a href="https://doi.org/10.1111%2Fj.1755-148X.2008.00505.x" target="_blank">https://doi.org/10.1111%2Fj.1755-148X.2008.00505.x</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Mazar J, DeYoung K, Khaitan D, Meister E, Almodovar A, Goydos J, Ray A, Perera RJ (2010). "The regulation of miRNA-211 expression and its role in melanoma cell invasiveness". PLOS ONE. 5 (11): e13779. Bibcode:2010PLoSO...513779M. doi:10.1371/journal.pone.0013779. PMC 2967468. PMID 21072171. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967468" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967468</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Levy C, Khaled M, Iliopoulos D, Janas MM, Schubert S, Pinner S, Chen PH, Li S, Fletcher AL, Yokoyama S, Scott KL, Garraway LA, Song JS, Granter SR, Turley SJ, Fisher DE, Novina CD (2010). "Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma". Mol Cell. 40 (5): 841–9. doi:10.1016/j.molcel.2010.11.020. PMC 3004467. PMID 21109473. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004467" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004467</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Audo I, Kohl S, Leroy BP, Munier FL, Guillonneau X, Mohand-Saïd S, Bujakowska K, Nandrot EF, Lorenz B, Preising M, Kellner U, Renner AB, Bernd A, Antonio A, Moskova-Doumanova V, Lancelot ME, Poloschek CM, Drumare I, Defoort-Dhellemmes S, Wissinger B, Léveillard T, Hamel CP, Schorderet DF, De Baere E, Berger W, Jacobson SG, Zrenner E, Sahel JA, Bhattacharya SS, Zeitz C (Nov 2009). "TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness". American Journal of Human Genetics. 85 (5): 720–9. doi:10.1016/j.ajhg.2009.10.013. PMC 2775830. PMID 19896113. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775830" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775830</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Li Z, Sergouniotis PI, Michaelides M, Mackay DS, Wright GA, Devery S, Moore AT, Holder GE, Robson AG, Webster AR (Nov 2009). "Recessive mutations of the gene TRPM1 abrogate ON bipolar cell function and cause complete congenital stationary night blindness in humans". American Journal of Human Genetics. 85 (5): 711–9. doi:10.1016/j.ajhg.2009.10.003. PMC 2775833. PMID 19878917. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775833" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775833</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>Nakamura M, Sanuki R, Yasuma TR, Onishi A, Nishiguchi KM, Koike C, Kadowaki M, Kondo M, Miyake Y, Furukawa T (2010). "TRPM1 mutations are associated with the complete form of congenital stationary night blindness". Molecular Vision. 16: 425–37. PMC 2838739. PMID 20300565. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838739" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838739</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> <li id="fn:18"><p>van Genderen MM, Bijveld MM, Claassen YB, Florijn RJ, Pearring JN, Meire FM, McCall MA, Riemslag FC, Gregg RG, Bergen AA, Kamermans M (Nov 2009). "Mutations in TRPM1 are a common cause of complete congenital stationary night blindness". American Journal of Human Genetics. 85 (5): 730–6. doi:10.1016/j.ajhg.2009.10.012. PMC 2775826. PMID 19896109. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775826" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775826</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></p></li> <li id="fn:19"><p>Bellone RR, Brooks SA, Sandmeyer L, Murphy BA, Forsyth G, Archer S, Bailey E, Grahn B (Aug 2008). "Differential gene expression of TRPM1, the potential cause of congenital stationary night blindness and coat spotting patterns (LP) in the Appaloosa horse (Equus caballus)". Genetics. 179 (4): 1861–70. doi:10.1534/genetics.108.088807. PMC 2516064. PMID 18660533. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516064" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516064</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></p></li> </ol>