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 tha...
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MDPI AG
2021-10-01
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| Series: | Current Issues in Molecular Biology |
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| author | Leonardo Vinícius Monteiro de Assis Maria Nathália Moraes Davi Mendes Matheus Molina Silva Carlos Frederico Martins Menck Ana Maria de Lauro Castrucci |
| author_facet | Leonardo Vinícius Monteiro de Assis Maria Nathália Moraes Davi Mendes Matheus Molina Silva Carlos Frederico Martins Menck Ana Maria de Lauro Castrucci |
| author_sort | Leonardo Vinícius Monteiro de Assis |
| collection | DOAJ |
| description | 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 <i>Opn4</i><sup>KO</sup> melanocytes displayed a faster proliferation rate compared to <i>Opn4</i><sup>WT</sup> melanocytes. Cell cycle population analysis demonstrated that OPN4<sup>KO</sup> melanocytes exhibited a faster cell cycle progression with reduced G<sub>0</sub>–G<sub>1</sub><b>,</b> and highly increased S and slightly increased G<sub>2</sub>/M cell populations compared to the <i>Opn4</i><sup>WT</sup> counterparts. Expression of specific cell cycle-related genes in <i>Opn4</i><sup>KO</sup> 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 <i>Opn4</i><sup>KO</sup> melanocytes compared to <i>Opn4</i><sup>WT</sup> cells. Interestingly, the gene expression of microphthalmia-associated transcription factor (MITF) was upregulated in <i>Opn4</i><sup>KO</sup> 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. |
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| series | Current Issues in Molecular Biology |
| spelling | doaj.art-ace813c0ee7b49eb9cc9bfd3af88b86b2023-11-23T07:43:39ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452021-10-014331436145010.3390/cimb43030101Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine MelanocytesLeonardo Vinícius Monteiro de Assis0Maria Nathália Moraes1Davi Mendes2Matheus Molina Silva3Carlos Frederico Martins Menck4Ana Maria de Lauro Castrucci5Laboratory of Comparative Physiology of Pigmentation, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo 05508-090, BrazilLaboratory of Comparative Physiology of Pigmentation, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo 05508-090, BrazilDNA Repair Lab, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, BrazilDNA Repair Lab, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, BrazilDNA Repair Lab, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, BrazilLaboratory of Comparative Physiology of Pigmentation, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo 05508-090, BrazilSkin 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 <i>Opn4</i><sup>KO</sup> melanocytes displayed a faster proliferation rate compared to <i>Opn4</i><sup>WT</sup> melanocytes. Cell cycle population analysis demonstrated that OPN4<sup>KO</sup> melanocytes exhibited a faster cell cycle progression with reduced G<sub>0</sub>–G<sub>1</sub><b>,</b> and highly increased S and slightly increased G<sub>2</sub>/M cell populations compared to the <i>Opn4</i><sup>WT</sup> counterparts. Expression of specific cell cycle-related genes in <i>Opn4</i><sup>KO</sup> 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 <i>Opn4</i><sup>KO</sup> melanocytes compared to <i>Opn4</i><sup>WT</sup> cells. Interestingly, the gene expression of microphthalmia-associated transcription factor (MITF) was upregulated in <i>Opn4</i><sup>KO</sup> 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.https://www.mdpi.com/1467-3045/43/3/101skin biologymelanocytesopsinsmelanopsinproliferation and cell cyclemolecular clock |
| spellingShingle | Leonardo Vinícius Monteiro de Assis Maria Nathália Moraes Davi Mendes Matheus Molina Silva Carlos Frederico Martins Menck Ana Maria de Lauro Castrucci Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes Current Issues in Molecular Biology skin biology melanocytes opsins melanopsin proliferation and cell cycle molecular clock |
| title | Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes |
| title_full | Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes |
| title_fullStr | Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes |
| title_full_unstemmed | Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes |
| title_short | Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes |
| title_sort | loss of melanopsin opn4 leads to a faster cell cycle progression and growth in murine melanocytes |
| topic | skin biology melanocytes opsins melanopsin proliferation and cell cycle molecular clock |
| url | https://www.mdpi.com/1467-3045/43/3/101 |
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