Spatial sequestration of misfolded proteins by a dynamic chaperone pathway enhances cellular fitness during stress.

ABSTRACT: The extensive links between proteotoxic stress, protein aggregation and pathologies ranging from ageing to neurodegeneration underscore the importance of understanding how cells manage protein misfolding. Using live-cell imaging, we determine the fate of stress-induced misfolded proteins from their initial appearance until their elimination. Upon denaturation, misfolded proteins are sequestered from the bulk cytoplasm into dynamic endoplasmic reticulum (ER)-associated puncta that move and coalesce into larger structures in an energy-dependent but cytoskeleton-independent manner. These puncta, which we name Q-bodies, concentrate different misfolded and stress-denatured proteins en route to degradation, but do not contain amyloid aggregates, which localize instead to the insoluble protein de

SUBMITTER: Escusa-Toret S 

PROVIDER: S-EPMC4121856 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature