Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Photochem Photobiol. 2020 Jan;96(1):83-93. doi: 10.1111/php.13178. Epub 2020 Jan 10.
G protein-coupled receptors (GPCRs) are core switches connecting excellular survival or death signals with cellular signaling pathways in a context-dependent manner. Opsin 3 (OPN3) belongs to the GPCR superfamily. However, whether OPN3 can control the survival or death of human melanocytes is not known. Here, we try to investigate the inherent function of OPN3 on the survival of melanocytes. Our results demonstrate that OPN3 knockdown by RNAi-OPN3 in human epidermal melanocytes leads to cell apoptosis. The downregulation of OPN3 markedly reduces intracellular calcium levels and decreases phosphorylation of BAD. Attenuated BAD phosphorylation and elevated BAD protein level alter mitochondria membrane permeability, which trigger activation of BAX and inhibition of BCL-2 and raf-1. Activated BAX results in the release of cytochrome c and the loss of mitochondrial membrane potential. Cytochrome c complexes associate with caspase 9, forming a postmitochondrial apoptosome that activate effector caspases including caspase 3 and caspase 7. The release of apoptotic molecules eventually promotes the occurrence of apoptosis. In conclusion, we hereby are the first to prove that OPN3 is a key signal responsible for cell survival through a calcium-dependent G protein-coupled signaling and mitochondrial pathway.
G 蛋白偶联受体（GPCRs）是一种核心开关，能够以依赖于上下文的方式将细胞外的存活或死亡信号与细胞信号通路连接起来。视蛋白 3（OPN3）属于 GPCR 超家族。然而，OPN3 是否能够控制人类黑素细胞的存活或死亡尚不清楚。在这里，我们试图研究 OPN3 对黑素细胞存活的固有功能。我们的结果表明，RNAi-OPN3 敲低人表皮黑素细胞中的 OPN3 会导致细胞凋亡。OPN3 的下调显著降低细胞内钙离子水平，并降低 BAD 的磷酸化。BAD 磷酸化减弱和 BAD 蛋白水平升高改变线粒体膜通透性，从而触发 BAX 的激活和 BCL-2 和 raf-1 的抑制。激活的 BAX 导致细胞色素 c 的释放和线粒体膜电位的丧失。细胞色素 c 复合物与 caspase 9 结合，形成线粒体后凋亡体，激活效应半胱天冬酶，包括 caspase 3 和 caspase 7。凋亡分子的释放最终促进了细胞凋亡的发生。总之，我们首次证明 OPN3 通过钙依赖性 G 蛋白偶联信号和线粒体途径是负责细胞存活的关键信号。
