期刊
MOLECULAR CELL
卷 63, 期 5, 页码 796-810出版社
CELL PRESS
DOI: 10.1016/j.molcel.2016.07.021
关键词
-
资金
- DFG-Center for Regenerative Therapies
- AriSLA
- MIUR
- Ministry of Health
- JPND
- European Union [643417]
Stress granules (SGs) are ribonucleoprotein complexes induced by stress. They sequester mRNAs and disassemble when the stress subsides, allowing translation restoration. In amyotrophic lateral sclerosis (ALS), aberrant SGs cannot disassemble and therefore accumulate and are degraded by autophagy. However, the molecular events causing aberrant SG formation and the molecular players regulating this transition are largely unknown. We report thatdefective ribosomal products (DRiPs) accumulate in SGs and promote a transition into an aberrant state that renders SGs resistant to RNase. We show that only a minor fraction of aberrant SGs is targeted by autophagy, whereas the majority disassembles in a process that requires assistance by the HSPB8BAG3-HSP70chaperone complex. We further demonstrate thatHSPB8-BAG3-HSP70ensures the functionality of SGs and restores proteostasis by targeting DRiPs for degradation. We propose a system of chaperone-mediated SG surveillance, or granulostasis, which regulates SG composition and dynamics and thus may play an important role in ALS.
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