Please use this identifier to cite or link to this item:
|Title:||Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1||Authors:||Nucifora F.C.
|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|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
|ncomms11792.pdf||1.36 MB||Adobe PDF|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.