Journal
JOURNAL OF CELL BIOLOGY
Volume 213, Issue 2, Pages 229-241Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201511024
Keywords
-
Categories
Funding
- National Institute of Neurological Disorders and Stroke [NS42842]
- National Institutes of Health predoctoral grant [2T32HG000044-16]
- Israel Science Foundation [1759/14]
- Israel Ministry of Health [3-100-39]
Ask authors/readers for more resources
Inclusion bodies (IBs) containing aggregated disease-associated proteins and polyubiquitin (poly-Ub) conjugates are universal histopathological features of neurodegenerative diseases. Ub has been proposed to target proteins to IBs for degradation via autophagy, but the mechanisms that govern recruitment of ubiquitylated proteins to IBs are not well understood. In this paper, we use conditionally destabilized reporters that undergo misfolding and ubiquitylation upon removal of a stabilizing ligand to examine the role of Ub conjugation in targeting proteins to IBs that are composed of an N-terminal fragment of mutant huntingtin, the causative protein of Huntington's disease. We show that reporters are excluded from IBs in the presence of the stabilizing ligand but are recruited to IBs after ligand washout. However, we find that Ub conjugation is not necessary to target reporters to IBs. We also report that forced Ub conjugation by the Ub fusion degradation pathway is not sufficient for recruitment to IBs. Finally, we find that reporters and Ub conjugates are stable at IBs. These data indicate that compromised folding states, rather than conjugation to Ub, can specify recruitment to IBs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available