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Context‐dependent and Disease‐specific Diversity in Stress Granules Formed from Pre‐existing Protein Interactions
Ist Teil von
The FASEB journal, 2018-04, Vol.32 (S1), p.252.3-252.3
Ort / Verlag
The Federation of American Societies for Experimental Biology
Erscheinungsjahr
2018
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
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 APEX proximity labeling, mass spectrometry and immunofluorescence to identify ~150 previously unknown human SG components. SG proteins form a dense interaction network in unstressed cells, facilitating rapid coalescence into larger SGs. About 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 ALS patients. Using three Drosophila ALS/FTD models, we identify ~30 SG‐associated modifiers of neurotoxicity in vivo. Altogether, our results highlight SG proteins as central to understanding and ultimately targeting neurodegeneration.
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.