Metacaspase Yca1 is required for clearance of insoluble protein aggregates.
In complex organisms, caspase proteases mediate a variety of cell behaviors, including proliferation, differentiation, and programmed cell death/apoptosis. Structural homologs to the caspase family (termed metacaspases) engage apoptosis in single-cell eukaryotes, yet the molecular mechanisms that contribute to nondeath roles are currently undefined. Here, we report an unexpected role for the Saccharomyces cerevisiae metacaspase Yca1 in protein quality control. Quantitative proteomic analysis of Deltayca1 cells identified significant alterations to vacuolar catabolism and stress-response proteins in the absence of induced stress. Yca1 protein complexes are enriched for aggregate-remodeling chaperones that colocalize with Yca1-GFP fusions. Finally, deletion and inactivation mutants of Yca1 accrue protein aggregates and autophagic bodies during log-phase growth. Together, our results show that Yca1 contributes to the fitness and adaptability of growing yeast through an aggregate remodeling activity.
Lee
Robin E C
RE
Ottawa Hospital Research Institute, Sprott Centre for Stem Cell Research, Ottawa Hospital, and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8L6.
Brunette
Steve
S
Puente
Lawrence G
LG
Megeney
Lynn A
LA
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D008954:Models, Biological; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism
D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; D049452:Green Fluorescent Proteins; D020169:Caspases; C456272:MCA1 protein, S cerevisiae