Aggresomes do not represent a general cellular response to protein misfolding in mammalian cells.

Department of Biochemistry, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada. simon.beaudoin@usherbrooke.ca

BACKGROUND: Aggresomes are juxtanuclear inclusion bodies that have been proposed to represent a general cellular response to misfolded proteins in mammalian cells. Yet, why aggresomes are not a pathological characteristic of protein misfolding diseases is unclear. Here, we investigate if a misfolded protein inevitably forms aggresomes in mammalian cells. RESULTS: We show that a cytoplasmic form of the prion protein may form aggresomes or dispersed aggregates in different cell lines. In contrast to aggresomes, the formation of dispersed aggregates is insensitive to histone deacetylase 6 inhibitors and does not result in cytoskeleton rearrangements. Modulation of expression levels or proteasome inhibitors does not alter the formation of dispersed aggregates. CONCLUSION: Our results establish that aggresomes are not obligatory products of protein misfolding in vivo.

PMID: 18937858 [PubMed - indexed for MEDLINE]

PMCID: PMC2576168