Turakhiya A, Meyer SR, Marincola G, Böhm S, Vanselow JT, Schlosser A, Hofmann K, Buchberger A. ZFAND1 Recruits p97 and the 26S Proteasome to Promote the Clearance of Arsenite-Induced Stress Granules. Mol Cell. 2018 Jun 7;70(5):906-919.e7. Epub 2018 May 24 PubMed.
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Boston University School of Medicine
I found this article to be very interesting. We have known that VCP mediates stress granule removal, but the mechanics of this are poorly understand. This manuscript very nicely highlights the role of a protein that appears to function as something like a VCP adapter protein. Importantly, they show that removal of ZFAND1 prevents removal of preformed stress granules (e.g., those formed by TIA1 or FMRP) after arsenite treatment. So the basics of the paper show some nice detailed cell biology. The paper also includes two very interesting extra pieces of information that hint at the complexity of stress granule biology. First, they note that ZFAND1 plays a role in removal of stress granules induced by arsenite, but not heat shock. This very nicely highlights the complexity of RNA granules generally, and stress granules in particular. Proteomics data suggest that stress granules differ by cell type, and this work very nicely highlights physiological differences too—as observed through the lens of ZFAND1-mediated removal. The second pearl of wisdom comes from the analysis of stress granules that remain in the absence of ZFAND1. These stress granules are targeted for removal by autophagy. This observation highlights the different roles played by the proteosome and autolysosomal system in stress granule removal, where the proteasome appears to remove small, dynamic stress granules formed after an acute stress, while the autolysosomal system removes the large, stable stress granules—which I refer to as pathological stress granules (these are what likely accumulate in neurodegenerative diseases).
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