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Heteromeric MT1/MT2 Melatonin Receptors Modulate Photoreceptor Function

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Science Signaling  08 Oct 2013:
Vol. 6, Issue 296, pp. ra89
DOI: 10.1126/scisignal.2004302

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In the retina, melatonin increases photoreceptor sensitivity to light at night, but not in mice deficient in the melatonin receptor MT1. Baba et al. found that two melatonin receptors, the G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) MT1 and MT2, were both present in the photoreceptor cells of mice, and, when coexpressed in cultured cells, these receptors formed homomeric and heteromeric complexes. Mice deficient in MT2 or expressing a mutant form of MT2 failed to respond to melatonin, suggesting that MT1 and MT2 may function as a heteromeric complex to mediate this response. By testing the response in the presence of various pharmacological agents, melatonin mediated its effect on photoreceptor responses in vivo through the inositol trisphosphate to protein kinase C pathway. Thus, this study delineates a pathway by which melatonin affects vision and provides in vivo evidence for functional GPCR heteromers.

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