Abstract：The TMEM106B protein is a type-II transmembrane protein, which localizes in the endosome and lysosome of dendrites in primary neurons. TMEM106B is essential for maintaining and branching of dendrites, and thus regulates retrograde lysosomal trafficking of dendrites in primary neurons. Mammalian melanocytes are derived from neural cells, while melanosomes are originated from early endosome. However, the function of TMEM106B protein in melanocytes and its potential molecular mechanism in melanogenesis still remain unknown. Recently it was reported that transcription factor EB (TFEB) was the regulator of lysosome synthesis and TMEM106B protein overexpression promoted TFEB translocation into the nucleus. However, MITF (microphthalmia-associated transcription factor) and TFEB regulate each other in melanoma cells in vitro. Here in, plasmid containing gene for TMEM106B overexpression was transfected into melanocytes to investigate the regulation of TMEM106B on melanogenesis. The results showed that TMEM106B protein was localized in the cytoplasm of melanocytes. Compared with the negative control (NC), the mRNA levels of cyclic AMP-responsive element-binding protein (CREB) and MITF, especially CREB, were significantly increased in melanocytes with TMEM106B overexpression P<0.001). Western blot analysis showed that the expression of phosphorylated MAP kinase (p-ERK) was apparently increased(P<0.001) and resulted in the up-regulation of melanogenic regulatory proteins, including MITF, tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1) and 2 (TYRP2). Masson-Fontana method showed that TMEM106B influenced the production of melanin in melanocytes. The spectrophotometry assay indicated that the amount of total melanin (ASM) (P<0.001) and eumelanin (EM)(P<0.05) were increased in alpaca melanocytes transfected with TMEM106B, while pheomelanin (PM) (P<0.001) was decreased. These results demonstrated that TMEM106B played a vital role in melanogenesis in melanocytes by regulating ERK/CREB signaling pathway.
周兆琦, Ajab Khan, 贾琼, 胡世雄, 范瑞文. 跨膜蛋白106B 通过ERK/CREB信号通路调控黑色素生成[J]. 中国生物化学与分子生物学报, 2021, 37(10): 1386-1393.
ZHOU Zhao-Qi, Ajab Khan, JIA Qiong, HU Shi-Xiong, FAN Rui-Wen. TMEM106B Induces Melanogenesis by Regulating ERK/CREB Signaling Pathway. Chinese Journal of Biochemistry and Molecular Biol, 2021, 37(10): 1386-1393.
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