期刊
JOURNAL OF CELL BIOLOGY
卷 191, 期 1, 页码 155-168出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201002100
关键词
-
类别
资金
- Telethon Foundation
- Advanced Imaging Research Center
- Italian Ministry of University and Research
- Italian Ministry of Health
- European Union
- Compagnia di San Paolo
Autophagy is an evolutionary conserved catabolic process involved in several physiological and pathological processes such as cancer and neuro-degeneration. Autophagy initiation signaling requires both the ULK1 kinase and the BECLIN 1-VPS34 core complex to generate autophagosomes, double-membraned vesicles that transfer cellular contents to lysosomes. In this study, we show that the BECLIN 1-VPS34 complex is tethered to the cytoskeleton through an interaction between the BECLIN 1-interacting protein AMBRA1 and dynein light chains 1/2. When autophagy is induced, ULK1 phosphorylates AMBRA1, releasing the autophagy core complex from dynein. Its subsequent relocalization to the endoplasmic reticulum enables autophagosome nucleation. Therefore, AMBRA1 constitutes a direct regulatory link between ULK1 and BECLIN 1-VPS34, which is required for core complex positioning and activity within the cell. Moreover, our results demonstrate that in addition to a function for microtubules in mediating autophagosome transport, there is a strict and regulatory relationship between cytoskeleton dynamics and autophagosome formation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据