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

Leonardo Vinícius Monteiro de Assis*, Maria Nathália Moraes, Davi Mendes, Matheus Molina Silva, Carlos Frederico Martins Menck, Ana Maria de Lauro Castrucci

*Corresponding author for this work


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 Opn4KO melanocytes displayed a faster proliferation rate compared to Opn4WT melanocytes. Cell cycle population analysis demonstrated that OPN4KO 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 Opn4WT counterparts. Expression of specific cell cycle-related genes in Opn4KO 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 Opn4KO melanocytes compared to Opn4WT cells. Interestingly, the gene expression of microphthalmia-associated transcription factor (MITF) was upregulated in Opn4KO 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.

Original languageEnglish
JournalCurrent Issues in Molecular Biology
Issue number3
Pages (from-to)1436-1450
Number of pages15
Publication statusPublished - 12.2021

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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