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Brief Communication

Nature Neuroscience 9, 1231–1233 (1 October 2006) | doi:10.1038/nn1776

Kinase activity of mutant LRRK2 mediates neuronal toxicity

Wanli W Smith , Zhong Pei , Haibing Jiang , Valina L Dawson , Ted M Dawson & Christopher A Ross

Mutations in the the leucine-rich repeat kinase-2 (LRRK2) gene cause autosomal-dominant Parkinson disease and some cases of sporadic Parkinson disease. Here we found that LRRK2 kinase activity was regulated by GTP via the intrinsic GTPase Roc domain, and alterations of LRRK2 protein that reduced kinase activity of mutant LRRK2 correspondingly reduced neuronal toxicity.