The toxicity of an "artificial" amyloid is related to how it interacts with membranes.
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.
IBGC, UMR 5095, CNRS, Université Bordeaux 2 Victor Segalen, Bordeaux, France.
Julien
J
Couthouis
Christelle
C
Marchal
Fabien
F
D'Angelo
Karine
K
Berthelot
Christophe
C
Cullin
D000682:Amyloid / Q000633:toxicity*; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism*; D055786:Gene Knockout Techniques; D005800:Genes, Fungal / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects; D008670:Metals / Q000494:pharmacology; D050296:Microbial Viability / Q000187:drug effects; D008954:Models, Biological; D011485:Protein Binding / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects* / Q000235:genetics; D012492:Salts / Q000494:pharmacology; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism; D014617:Vacuoles / Q000187:drug effects / Q000235:genetics
D000682:Amyloid; D008670:Metals; D012492:Salts