Synaptotagmin‐4 promotes dendrite extension and melanogenesis in alpaca melanocytes by regulating Ca 2+ influx via TRPM1 channels

作者：Qiong Jia, Shixiong Hu, Dingxing Jiao, Xiuqing Li, Shuhui Qi, Ruiwen Fan · 发表于：Cell Biochemistry and Function · 年份：2019 · DOI：10.1002/cbf.3465 · 被引用次数：28 · 研究领域：melanin and skin pigmentation、Biochemical Analysis and Sensing Techniques、Regulation of Appetite and Obesity

Synaptotagmin‐4 (SYT4) is a membrane protein that regulates membrane traffic in neurons in a calcium‐dependent or calcium‐independent manner. In melanocytes, the intracellular free calcium ion (Ca 2+ ) may be important for dendrite growth and melanogenesis. Mammalian melanocytes originating from neural crest cells produce melanins. Therefore, we predicted that SYT4 might play a role in melanogenesis and the dendrite morphology of melanocytes. To investigate whether SYT4 is involved in melanocyte physiology, SYT4 was overexpressed in alpaca melanocytes and B16‐F10 cells. The results showed that SYT4 overexpression resulted in a phenotype consistent with melanogenesis and dendrite extension. At the molecular level, SYT4 interacted with extracellular regulated MAP kinase (ERK) to decrease p‐ERK activity, which negatively regulated CREB expression. Furthermore, cyclic AMP‐responsive element‐binding protein (CREB) was upregulated and caused the downregulation of the expression of melanogenic regulatory proteins, including microphthalmia‐associated transcription factor (MITF), tyrosinase (TYR), tyrosinase‐related protein‐1 (TYRP1), dopachrome tautomerase (DCT), and transient receptor potential melastatin 1 (TRPM1). Intracellular free Ca 2+ promoted the upregulation of calcium/calmodulin dependent protein kinase IV (CAMK4) expression, which phosphorylated CREB (p‐CREB). In turn, p‐CREB participated in the transcription of MITF. These results demonstrated that SYT4 promoted melanogen...