Journal
CELL
Volume 172, Issue 3, Pages 590-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2017.12.032
Keywords
-
Categories
Funding
- Larry L. Hillblom Foundation [2014-A-027-FEL]
- IRCM Angelo Pizzagalli fellowship
- NIH Graduate Training in Cellular and Molecular Pharmacology Training Grant [T32 GM007752]
- ALS Canada/Brain Canada Discovery Grant
- NIH [R01NS101986, DP2GM119132, NS103172, HG004659]
- Packard Center for ALS Research
- Target ALS Foundation
- Hellman Fellowship
- ALS Association
Ask authors/readers for more resources
Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in the context of neurodegeneration-linked mutations, we used ascorbate peroxidase (APEX) proximity labeling, mass spectrometry, and immunofluorescence to identify similar to 150 previously unknown human SG components. A highly integrated, pre-existing SG protein interaction network in unstressed cells facilitates rapid coalescence into larger SGs. Approximately 20% of SG diversity is stress or cell-type dependent, with neuronal SGs displaying a particularly complex repertoire of proteins enriched in chaperones and autophagy factors. Strengthening the link between SGs and neurodegeneration, we demonstrate aberrant dynamics, composition, and subcellular distribution of SGs in cells from amyotrophic lateral sclerosis (ALS) patients. Using three Drosophila ALS/FTD models, we identify SG-associated modifiers of neurotoxicity in vivo. Altogether, our results highlight SG proteins as central to understanding and ultimately targeting neurodegeneration.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available