TY - JOUR
AU - Ross, Christopher A.
AB - 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.
TI - Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1
JF - Nature Communications
DO - 10.1038/ncomms11792
DA - 2016-06-07
UR - https://www.deepdyve.com/lp/springer-journals/ubiqutination-via-k27-and-k29-chains-signals-aggregation-and-neuronal-XD98JqWbjV
SP - 1
EP - 11
VL - 7
IS - 1
DP - DeepDyve
ER -