纤维的生物发生需要PMEL的C-mannosylation
Ryota Kawahara1, Tomoko Usami1, Satoko Arakawa2,3
1Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
The FEBS journal
|August 8, 2023
概括
前黑色素体蛋白 (PMEL) 的C-mannosylation对于黑色素体的发育至关重要. 修改PMEL的方法
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 葡萄糖科学 (Glycoscience) 是一种科学.
背景情况:
- 前黑色素蛋白 (PMEL) 对于黑色素的成熟和黑色素沉积至关重要.
- 翻译后的修改,包括糖化,调节PMEL功能.
- C-曼诺基化是一种罕见的糖基化,可能会影响蛋白质分泌和局部化.
研究的目的:
- 为了调查PMEL的C-曼诺基化.
- 确定PMEL C-mannosylation对黑色素体发育的功能影响.
主要方法:
- 在人类黑色素瘤细胞中的重组PMEL表达和净化.
- 质谱测量以确定C-mannosylation的部位.
- 在CRISPR/Cas9基因编辑中创建PMEL突变.
- 传输电子显微镜,西部污点和免疫光分析.
主要成果:
- 人类PMEL在其核心粉样蛋白片段和N端片段的多重托残留处被C-曼诺基化.
- 在W104中C-mannosylated托的突变显著减少了含有纤维的黑色素体.
- W104F突变导致ER保留,错误折叠,并减少功能纤维的形成.
结论:
- 对于正常的黑色素体发育来说,PMEL的C-mannosylation是至关重要的.
- PMEL C-曼诺基化调节PMEL衍生的粉样纤维的形成.
- 特定的C-mannosylation位点,如W104,对于PMEL在黑色素生成中的作用至关重要.
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