LRRK2 substrate workgroup

Mutations within PARK8 (LRRK2/dardarin) are associated with autosomal dominant familial PD. LRRK2 contains multiple protein-binding domains and catalytic domains, including a Roc-GTPase domain and a kinase domain similar to both receptor-interacting kinases and tyrosine kinases.

Its function remains elusive, and mutations are found within many regions of the gene (though the G2019S mutation is most common). This mutation leads to a gain-of-function in the kinase activity of LRRK2. Several studies demonstrate that this increased kinase activity can lead to cell death, dependent on GTP binding to the Roc-GTPase domain (Thomas et al., 2007; Ito et al., 2007).

This group will explore discovery around the substrates of LRRK2.