Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes

• Published in: Current issues in molecular biology Vol. 43; no. 3; pp. 1436 - 1450
• Main Authors: de Assis, Leonardo Vinícius Monteiro, Moraes, Maria Nathália, Mendes, Davi, Silva, Matheus Molina, Menck, Carlos Frederico Martins, Castrucci, Ana Maria de Lauro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 04.10.2021; MDPI AG
• Subjects: Animals; Biomarkers; Cell Cycle - drug effects; Cell Cycle - genetics; Cell Cycle Proteins - genetics; Cell Proliferation; Cells, Cultured; CLOCK Proteins - genetics; Flow Cytometry; Gene Expression Regulation - drug effects; Gene Knockout Techniques; melanocytes; Melanocytes - drug effects; Melanocytes - metabolism; melanopsin; Mice; molecular clock; opsins; proliferation and cell cycle; Rod Opsins - deficiency; Skin - cytology; Skin - metabolism; skin biology; melanopsin; melanocytes; molecular clock; skin biology; opsins; proliferation and cell cycle
• ISSN: 1467-3045; 1467-3037; 1467-3045
• DOI: 10.3390/cimb43030101

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 melanocytes displayed a faster proliferation rate compared to melanocytes. Cell cycle population analysis demonstrated that OPN4 melanocytes exhibited a faster cell cycle progression with reduced G -G and highly increased S and slightly increased G /M cell populations compared to the counterparts. Expression of specific cell cycle-related genes in 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 melanocytes compared to cells. Interestingly, the gene expression of microphthalmia-associated transcription factor (MITF) was upregulated in 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.