The WD40 domain is required for LRRK2 neurotoxicity.

ABSTRACT:

Background

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson disease (PD). LRRK2 contains an "enzymatic core" composed of GTPase and kinase domains that is flanked by leucine-rich repeat (LRR) and WD40 protein-protein interaction domains. While kinase activity and GTP-binding have both been implicated in LRRK2 neurotoxicity, the potential role of other LRRK2 domains has not been as extensively explored.

Principal findings

We demonstrate that LRRK2 normally exists in a dimeric complex, and that removing the WD40 domain prevents complex formation and autophosphorylation. Moreover, loss of the WD40 domain completely blocks the neurotoxicity of multiple LRRK2 PD mutations.

Conclusion

These findings suggest that LRRK2 dimeriza

SUBMITTER: Jorgensen ND 

PROVIDER: S-EPMC2794542 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature