期刊
JOURNAL OF CELL BIOLOGY
卷 212, 期 5, 页码 577-590出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201503075
关键词
-
类别
资金
- National Institutes of Health [CA126792, CA188404, GM079139, S10 RR26758]
- Department of Defense Breast Cancer Research Program [W81XWH-11-1-0130, W81XWH-12-1-0505]
- Samuel Waxman Cancer Research Foundation
- National Institutes of Health Predoctoral Fellowship [F31CA167905]
- National Science Foundation Graduate Student Fellowship [DGE-1 144247]
Autophagy is a catabolic pathway involving the sequestration of cellular contents into a double-membrane vesicle, the autophagosome. Although recent studies have demonstrated that autophagy supports cell migration, the underlying mechanisms remain unknown. Using live-cell imaging, we uncover that autophagy promotes optimal migratory rate and facilitates the dynamic assembly and disassembly of cell-matrix focal adhesions (FAs), which is essential for efficient motility. Additionally, our studies reveal that autophagosomes associate with FAs primarily during disassembly, suggesting autophagy locally facilitates the destabilization of cell-matrix contact sites. Furthermore, we identify the selective autophagy cargo receptor neighbor of BRCA1 (NBR1) as a key mediator of autophagy-dependent FA remodeling. NBR 1 depletion impairs FA turnover and decreases targeting of autophagosomes to FAs, whereas ectopic expression of autophagy-competent, but not autophagy-defective, NBR1 enhances FA disassembly and reduces FA lifetime during migration. Our findings provide mechanistic insight into how autophagy promotes migration by revealing a requirement for NBR1-mediated selective autophagy in enabling FA disassembly in motile cells.
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