Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, 153-8902, Japan.
Laboratory of Pathology, Setsunan University, 45-1 Nagaotohge-cho, Hirakata, Osaka, Japan.
Sci Rep. 2021 Jul 2;11(1):13771. doi: 10.1038/s41598-021-93110-1.
Autophagy is a degradation process of cytoplasmic proteins and organelles trafficked to degradation vesicles known as autophagosomes. The conversion of LC3-I to LC3-II is an essential step of autophagosome formation, and FYCO1 is a LC3-binding protein that mediates autophagosome transport. The p62 protein also directly binds to LC3 and is degraded by autophagy. In the present study, we demonstrated that disrupting the FYCO1 gene in mice resulted in cataract formation. LC3 conversion decreased in eyes from FYCO1 knockout mice. Further, FYCO1 interacted with αA- and αB-crystallin, as demonstrated by yeast two-hybrid screening and immunoprecipitation analyses. In eyes from knockout mice, the soluble forms of αA- and αB-crystallin, the lens's major protein components, decreased. In addition, p62 accumulated in eyes from FYCO1 knockout mice. Collectively, these findings suggested that FYCO1 recruited damaged α-crystallin into autophagosomes to protect lens cells from cataract formation.
自噬是细胞质蛋白和细胞器被转运到称为自噬体的降解小泡的降解过程。LC3-I 向 LC3-II 的转化是自噬体形成的一个必要步骤，而 FYCO1 是一种介导自噬体运输的 LC3 结合蛋白。p62 蛋白也直接与 LC3 结合，并被自噬体降解。在本研究中，我们证明了在小鼠中破坏 FYCO1 基因会导致白内障形成。FYCO1 敲除小鼠眼睛中的 LC3 转化减少。此外，酵母双杂交筛选和免疫沉淀分析表明 FYCO1 与 αA-和 αB-晶状体蛋白相互作用。在敲除小鼠的眼睛中，晶状体的主要蛋白成分 αA-和 αB-晶状体蛋白的可溶性形式减少。此外，FYCO1 敲除小鼠的眼睛中 p62 积累。综上所述，这些发现表明 FYCO1 将受损的 α-晶状体蛋白募集到自噬体中，以保护晶状体细胞免受白内障形成。
