LRRK2通过丝状肌动蛋白解聚和Rac1抑制作用降低小胶质细胞的肌动蛋白动力学。
LRRK2 decreases microglial actin dynamics by filamentous actin depolymerization and Rac1 inhibition.
作者信息
Kim Beomsue, Suh Young Ho, Joe Eunhye
机构信息
Neural Circuit Research Group, Korea Brain Research Institute, Daegu, Republic of Korea.
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
出版信息
Anim Cells Syst (Seoul). 2022 Dec 22;26(6):380-387. doi: 10.1080/19768354.2022.2158219. eCollection 2022.
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.
活跃的肌动蛋白动力学是脑小胶质细胞的一个关键特征。在此我们报告，LRRK2，一种与家族性帕金森病相关的主要基因，对小胶质细胞的肌动蛋白动力学起负向调节作用。LRRK2通过直接结合丝状肌动蛋白（F-肌动蛋白）或抑制小胶质细胞的Rac-PAK信号传导来使其解聚。敲低LRRK2导致ADP激活的小胶质细胞的褶皱减少、片状伪足形成增强，改变了小胶质细胞向受损细胞积极迁移的生理活性。这些结果表明，LRRK2是小胶质细胞中受控制的肌动蛋白动力学的负调节因子。
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