{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:53:43Z","timestamp":1790967223354,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,3,27]],"date-time":"2013-03-27T00:00:00Z","timestamp":1364342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2013,5]]},"abstract":"Summary<\/jats:title>Mutations in TRPM<\/jats:styled-content>1, a calcium channel expressed in retinal bipolar cells and epidermal melanocytes, cause complete congenital stationary night blindness with no discernible skin phenotype. In the retina, TRPM<\/jats:styled-content>1 activity is negatively coupled to metabotropic glutamate receptor 6 (mG<\/jats:styled-content>luR<\/jats:styled-content>6) signaling through G<\/jats:styled-content>\u03b1<\/jats:italic>o<\/jats:sub> and TRPM<\/jats:styled-content>1 mutations result in the loss of responsiveness of TRPM<\/jats:styled-content>1 to mG<\/jats:styled-content>luR<\/jats:styled-content>6 signaling. Here, we show that human melanocytes express mG<\/jats:styled-content>luR<\/jats:styled-content>6, and treatment of melanocytes with L<\/jats:styled-content>\u2010AP<\/jats:styled-content>4, a type III mG<\/jats:styled-content>luR<\/jats:styled-content>\u2010selective agonist, enhances C<\/jats:styled-content>a2+<\/jats:sup> uptake. Knockdown of TRPM<\/jats:styled-content>1 or mG<\/jats:styled-content>luR<\/jats:styled-content>6 by shRNA<\/jats:styled-content> abolished L<\/jats:styled-content>\u2010AP<\/jats:styled-content>4\u2010induced C<\/jats:styled-content>a2+<\/jats:sup> influx and TRPM<\/jats:styled-content>1 currents, showing that TRPM<\/jats:styled-content>1 activity in melanocytes is positively coupled to mG<\/jats:styled-content>luR<\/jats:styled-content>6 signaling. G<\/jats:styled-content>\u03b1<\/jats:italic>o<\/jats:sub> protein is absent in melanocytes. However, forced expression of G<\/jats:styled-content>\u03b1<\/jats:italic>o<\/jats:sub> restored negative coupling of TRPM<\/jats:styled-content>1 to mG<\/jats:styled-content>luR<\/jats:styled-content>6 signaling, but treatment with pertussis toxin, an inhibitor of Gi<\/jats:sub>\/Go<\/jats:sub> proteins, did not affect basal or mG<\/jats:styled-content>luR<\/jats:styled-content>6\u2010induced C<\/jats:styled-content>a2+<\/jats:sup> uptake. Additionally, chronic stimulation of mG<\/jats:styled-content>luR<\/jats:styled-content>6 altered melanocyte morphology and increased melanin content. These data suggest differences in coupling of TRPM<\/jats:styled-content>1 function to mG<\/jats:styled-content>luR6 signaling explain different cellular responses to glutamate in the retina and the skin.<\/jats:p>","DOI":"10.1111\/pcmr.12083","type":"journal-article","created":{"date-parts":[[2013,3,2]],"date-time":"2013-03-02T04:18:42Z","timestamp":1362197922000},"page":"348-356","source":"Crossref","is-referenced-by-count":42,"title":["Metabotropic glutamate receptor 6 signaling enhances TRPM<\/scp>1 calcium channel function and increases melanin content in human melanocytes"],"prefix":"10.1111","volume":"26","author":[{"given":"Sulochana","family":"Devi","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogananda","family":"Markandeya","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nityanand","family":"Maddodi","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Dhingra","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noga","family":"Vardi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi C.","family":"Balijepalli","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijayasaradhi","family":"Setaluri","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.10.013"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.108.088807"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/elq002"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/317538a0"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00092.2009"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-24-09053.2000"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-12-04878.2002"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1436-12.2012"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(200006)183:3<364::AID-JCP9>3.0.CO;2-X"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/319670a0"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2005.00284.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21639"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/353043a0"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2010.08.004"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912730107"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.202945"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.10.003"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2005.05.018"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi700338m"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1523\/JNEUROSCI.18-05-01735.1998","article-title":"Effect of glutamate on dendritic growth in embryonic rat motoneurons","volume":"18","author":"Metzger F.","year":"1998","journal-title":"J. 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