The toxicity of an “artificial” amyloid is related to how it interacts with membranes

IBGC, UMR 5095, CNRS, Université Bordeaux 2 Victor Segalen, Bordeaux, France.
Prion (Impact Factor: 2.24). 10/2010; 4(4):283-91. DOI: 10.4161/pri.4.4.13126
Source: PubMed


Despite intensive research into how amyloid structures can impair cellular viability, the molecular nature of these toxic species and the cellular mechanisms involved are not clearly defined and may differ from one disease to another. We systematically analyzed, in Saccharomyces cerevisiae, genes that increase the toxicity of an amyloid (M8), previously selected in yeast on the sole basis of its cellular toxicity (and consequently qualified as "artificial"). This genomic screening identified the Vps-C HOPS (homotypic vacuole fusion and protein sorting) complex as a key-player in amyloid toxicity. This finding led us to analyze further the phenotype induced by M8 expression. M8-expressing cells displayed an identical phenotype to vps mutants in terms of endocytosis, vacuolar morphology and salt sensitivity. The direct and specific interaction between M8 and lipids reinforces the role of membrane formation in toxicity due to M8. Together these findings suggest a model in which amyloid toxicity results from membrane fission.

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Available from: Julien Couthouis, Sep 26, 2015
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    • "M8 is organized in amyloid nanofibers with a cross-beta core of antiparallel-β-sheets and presents particular oligomeric intermediates [42] [43]. Screening for yeast genes involved in M8 toxicity, we demonstrated that M8 toxicity was probably mediated through membranes by strongly interfering with vesicular trafficking in the yeast cells [44]. Preliminary results with Langmuir lipid monolayers showed that M8 was specifically interacting at the interface with negatively charged lipids [39] [45]. "
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