FIGURE 1.

Regulation of LRRK2 output by GTPase activity, GAPs and GEFs. RGS2 and ArhGEF7 both bind to LRRK2 and inhibit GTPase activity, which also inhibits LRRK2 kinase activity and appears to direct LRRK2 toward increasing neuronal cytoskeletal activity. Rac1 is a small GTPase known to regulate actin polymerase. Rac1 binds to LRRK2 and might act in concert with LRRK2 to increase cytoskeletal activity. In contrast, binding of ArfGAP1 to LRRK2 increases its autophosphorylation, which appears to inhibit cytoskeletal activity.