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Metabotropic glutamate receptor 6 signaling enhances TRPM 1 calcium channel function and increases melanin content in human melanocytes
Author(s) -
Devi Sulochana,
Markandeya Yogananda,
Maddodi Nityanand,
Dhingra Anuradha,
Vardi Noga,
Balijepalli Ravi C.,
Setaluri Vijayasaradhi
Publication year - 2013
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12083
Subject(s) - metabotropic glutamate receptor 6 , metabotropic glutamate receptor , metabotropic glutamate receptor 1 , microbiology and biotechnology , metabotropic glutamate receptor 5 , metabotropic glutamate receptor 7 , biology , metabotropic glutamate receptor 3 , chemistry , glutamate receptor , biochemistry , receptor
Summary Mutations in TRPM 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 1 activity is negatively coupled to metabotropic glutamate receptor 6 (m G lu R 6) signaling through G α o and TRPM 1 mutations result in the loss of responsiveness of TRPM 1 to m G lu R 6 signaling. Here, we show that human melanocytes express m G lu R 6, and treatment of melanocytes with L ‐ AP 4, a type III mG lu R ‐selective agonist, enhances C a 2+ uptake. Knockdown of TRPM 1 or m G lu R 6 by sh RNA abolished L ‐ AP 4‐induced C a 2+ influx and TRPM 1 currents, showing that TRPM 1 activity in melanocytes is positively coupled to m G lu R 6 signaling. G α o protein is absent in melanocytes. However, forced expression of G α o restored negative coupling of TRPM 1 to m G lu R 6 signaling, but treatment with pertussis toxin, an inhibitor of G i /G o proteins, did not affect basal or m G lu R 6‐induced C a 2+ uptake. Additionally, chronic stimulation of m G lu R 6 altered melanocyte morphology and increased melanin content. These data suggest differences in coupling of TRPM 1 function to m G luR6 signaling explain different cellular responses to glutamate in the retina and the skin.