Reversible, functional amyloids: towards an understanding of their regulation in yeast and humans

Cell Cycle
Gea CereghettiMatthias Peter

Abstract

Protein aggregates, and in particular amyloids, are generally considered to be inherently irreversible aberrant clumps, and are often associated with pathologies, such as Alzheimer's disease, Parkinson's disease, or systemic amyloidosis. However, recent evidence demonstrates that some aggregates are not only fully reversible, but also perform essential physiological functions. Despite these new findings, very little is known about how these functional protein aggregates are regulated in a physiological context. Here, we take the yeast pyruvate kinase Cdc19 as an example of a protein forming functional, reversible, solid, amyloid-like aggregates in response to stress conditions. Cdc19 aggregation is regulated via an aggregation-prone low complexity region (LCR). In favorable growth conditions, this LCR is prevented from aggregating by phosphorylation or oligomerization, while upon glucose starvation it becomes exposed and allows aggregation. We suggest that LCR phosphorylation, oligomerization or partner-binding may be general and widespread mechanisms regulating LCR-mediated reversible protein aggregation. Moreover, we show that, as predicted by computational tools, Cdc19 forms amyloid-like aggregates in vitro. Interestingly, w...Continue Reading

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Citations

Apr 21, 2020·Biochemical Society Transactions·Loes van Dam, Tobias B Dansen
May 2, 2020·Current Genetics·Aleksandra V Sergeeva, Alexey P Galkin
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Dec 1, 2020·Frontiers in Neuroscience·Xu YanXinwen Zhang
Mar 18, 2021·Chemical Communications : Chem Comm·Alessandra MontiNunzianna Doti

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Methods Mentioned

BETA
fluorescence recovery after photobleaching
fluorescence microscopy
circular
infrared
X-ray
nuclear magnetic resonance
fluorescence
flow cytometry
electron microscopy
light microscopy

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