LRRK2 decreases microglial actin dynamics by filamentous actin depolymerization and Rac1 inhibition.

An active actin dynamic is a crucial feature of brain microglia. Here we report that LRRK2, a primary familial Parkinson's disease-associated gene, negatively regulates microglia's actin dynamics. LRRK2 depolymerized filamentous actin (F-actin) by directly binding to it or inhibiting microglia's Rac-PAK signaling. LRRK2 knockdown resulted in a reduced ruffle and enhanced lamellipodia formation of ADP-activated microglia, altering the microglia's physiological activity to vigorous migration toward damaged cells. These results suggest that LRRK2 is a negative regulator for the controlled actin dynamics in microglia.