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

Beomsue Kim; Young Ho Suh; Eunhye Joe

doi:10.1080/19768354.2022.2158219

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

Anim Cells Syst (Seoul). 2022 Dec 22;26(6):380-387. doi: 10.1080/19768354.2022.2158219. eCollection 2022.

Authors

Beomsue Kim¹, Young Ho Suh², Eunhye Joe^{3

4

5}

Affiliations

¹ Neural Circuit Research Group, Korea Brain Research Institute, Daegu, Republic of Korea.
² Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
³ Department of Pharmacology, Ajou University School of Medicine, Suwon, Republic of Korea.
⁴ Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.
⁵ Center for Convergence Research of Neurological Disorders, Ajou University Schoo lof Medicine, Suwon, Republic of Korea.

Abstract

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.

Keywords: Actin depolymerization; F-actin-binding proteins; Leucine-rich repeat serine-threonine protein kinase-2; Parkinson disease 8; microglia.

Grants and funding

This research was supported by KBRI basic research program through Korea Brain Research Institute, funded by Ministry of Science and ICT (22-BR-01-03 and 22-BR-03-04), and by the Basic Science Research Program (NRF-2021R1A2C1013975) through the National Research Foundation of Korea to BK. The funders had no role in study design, data collection, analysis, publication decision, or manuscript preparation.