Loss of melanopsin (OPN4) leads to a faster cell cycle progression and growth in murine melanocytes

Skin melanocytes harbor a complex photosensitive system comprised of opsins, which were shown, in recent years, to display light-and thermo-independent functions. Based on this premise, we investigated whether melanopsin, OPN4, displays such a role in normal melanocytes. In this study, we found that murine Opn4^KO melanocytes displayed a faster proliferation rate compared to Opn4^WT melanocytes. Cell cycle population analysis demonstrated that OPN4^KO melanocytes exhibited a faster cell cycle progression with reduced G₀ –G₁, and highly increased S and slightly increased G₂ /M cell populations compared to the Opn4^WT counterparts. Expression of specific cell cycle-related genes in Opn4^KO melanocytes exhibited alterations that corroborate a faster cell cycle progression. We also found significant modification in gene and protein expression levels of important regulators of melanocyte physiology. PER1 protein level was higher while BMAL1 and REV-ERBα decreased in Opn4^KO melanocytes compared to Opn4^WT cells. Interestingly, the gene expression of microphthalmia-associated transcription factor (MITF) was upregulated in Opn4^KO melanocytes, which is in line with a higher proliferative capability. Taken altogether, we demonstrated that OPN4 regulates cell proliferation, cell cycle, and affects the expression of several important factors of the melanocyte physiology; thus, arguing for a putative tumor suppression role in melanocytes.