Abstract：
Myosin Va (Myo Va) is one of three protein complexes involved in melanosome transport. In this study, we identified BMP-2 as an up-regulator of Myo Va expression using 2-methyl-naphtho[1,2,3-de]quinolin-8-one (MNQO). Our results showed that MNQO reduced the mRNA and protein expression of Myo Va and BMP-2 in melanocytes. Knockdown of BMP-2 by siRNA also affected Myo Va mRNA and protein expression, confirming that MNQO regulates Myo Va through BMP-2. Furthermore, phosphorylation of Smad1/5/8 by BMP2 treatment confirmed that the BMP-2/Smad signaling pathway regulates Myo Va expression in Melan-a melanocytes. Smad-binding elements were found in the Myo Va promoter and phosphorylated Smad1/5/8 bind directly to the Myo Va promoter to activate Myo Va transcription and BMP-2 enhances this binding. These findings provide insight into a new role for BMP-2 in Melan-a melanocytes and a mechanism of regulation of Myo Va expression that may be beneficial in the treatment of albinism or hyperpigmentation disorders.
摘要：
肌球蛋白Va(MyoVa)是参与黑素体转运的三种蛋白质复合物之一。在这项研究中,我们使用2-甲基-萘并[1,2,3-de]喹啉-8-酮（MNQO）将BMP-2鉴定为MyoVa表达的上调因子。我们的结果表明，MNQO降低了黑素细胞中MyoVa和BMP-2的mRNA和蛋白表达。siRNA敲除BMP-2也影响MyoVamRNA和蛋白表达,确认MNQO通过BMP-2调节MyoVa。此外，通过BMP2处理的Smad1/5/8的磷酸化证实BMP-2/Smad信号通路调节Melan-a黑素细胞中MyoVa的表达。在MyoVa启动子中发现了Smad结合元件，磷酸化的Smad1/5/8直接与MyoVa启动子结合以激活MyoVa转录，而BMP-2增强了这种结合。这些发现为BMP-2在Melan-a黑素细胞中的新作用以及MyoVa表达的调节机制提供了见解，这可能有益于白化病或色素沉着过度疾病的治疗。
