生物
应力颗粒
袋3
蛋白质稳态
细胞生物学
伴侣(临床)
自噬
核糖核蛋白
遗传学
核糖核酸
翻译(生物学)
信使核糖核酸
基因
医学
病理
细胞凋亡
作者
Massimo Ganassi,Daniel Matějů,Ilaria Bigi,Laura Mediani,Ina Poser,Hyun O. Lee,Samuel J. Seguin,Federica Morelli,Jonathan Vinet,Giuseppina Leo,Orietta Pansarasa,Cristina Cereda,Angelo Poletti,Simon Alberti,Serena Carra
出处
期刊:Molecular Cell
[Elsevier]
日期:2016-09-01
卷期号:63 (5): 796-810
被引量:229
标识
DOI:10.1016/j.molcel.2016.07.021
摘要
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 that defective 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 HSPB8-BAG3-HSP70 chaperone complex. We further demonstrate that HSPB8-BAG3-HSP70 ensures 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.
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