Journal
ANIMAL CELLS AND SYSTEMS
Volume 26, Issue 6, Pages 380-387Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/19768354.2022.2158219
Keywords
Actin depolymerization; F-actin-binding proteins; Leucine-rich repeat serine-threonine protein kinase-2; Parkinson disease 8; microglia
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LRRK2, a primary familial Parkinson's disease-associated gene, negatively regulates microglia's actin dynamics by directly binding to or inhibiting microglia's Rac-PAK signaling. Knockdown of LRRK2 alters microglia's physiological activity, leading to vigorous migration toward damaged cells.
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.
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