Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncomms11792
Title: Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1
Authors: Nucifora F.C.
Nucifora L.G.
Ng C.-H.
Arbez N.
Guo Y.
Roby E.
Shani V.
Engelender S.
Wei D.
Wang X.-F.
Li T.
Moore D.J.
Pletnikova O.
Troncoso J.C.
Sawa A.
Dawson T.M.
Smith W.
Lim K.-L. 
Ross C.A.
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Nucifora F.C., Nucifora L.G., Ng C.-H., Arbez N., Guo Y., Roby E., Shani V., Engelender S., Wei D., Wang X.-F., Li T., Moore D.J., Pletnikova O., Troncoso J.C., Sawa A., Dawson T.M., Smith W., Lim K.-L., Ross C.A. (2016). Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1. Nat. Commun. 7 : 11792. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms11792
Abstract: A common genetic form of Parkinson's disease (PD) is caused by mutations in LRRK2. We identify WSB1 as a LRRK2 interacting protein. WSB1 ubiquitinates LRRK2 through K27 and K29 linkage chains, leading to LRRK2 aggregation and neuronal protection in primary neurons and a Drosophila model of G2019S LRRK2. Knocking down endogenous WSB1 exacerbates mutant LRRK2 neuronal toxicity in neurons and the Drosophila model, indicating a role for endogenous WSB1 in modulating LRRK2 cell toxicity. WSB1 is in Lewy bodies in human PD post-mortem tissue. These data demonstrate a role for WSB1 in mutant LRRK2 pathogenesis, and suggest involvement in Lewy body pathology in sporadic PD. Our data indicate a role in PD for ubiquitin K27 and K29 linkages, and suggest that ubiquitination may be a signal for aggregation and neuronal protection in PD, which may be relevant for other neurodegenerative disorders. Finally, our study identifies a novel therapeutic target for PD.
Source Title: Nat. Commun.
URI: http://scholarbank.nus.edu.sg/handle/10635/150086
ISSN: 20411723
DOI: 10.1038/ncomms11792
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