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

ABSTRACTAn 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 microgl...

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Main Authors: Beomsue Kim, Young Ho Suh, Eunhye Joe
Format: Article
Language:English
Published: Taylor & Francis Group 2022-11-01
Series:Animal Cells and Systems
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19768354.2022.2158219
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author Beomsue Kim
Young Ho Suh
Eunhye Joe
author_facet Beomsue Kim
Young Ho Suh
Eunhye Joe
author_sort Beomsue Kim
collection DOAJ
description ABSTRACTAn 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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spelling doaj.art-8141f10e750f4c7197cacb75f9e61cdb2023-05-31T05:33:12ZengTaylor & Francis GroupAnimal Cells and Systems1976-83542151-24852022-11-0126638038710.1080/19768354.2022.2158219LRRK2 decreases microglial actin dynamics by filamentous actin depolymerization and Rac1 inhibitionBeomsue Kim0Young Ho Suh1Eunhye Joe2Neural Circuit Research Group, Korea Brain Research Institute, Daegu, Republic of KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Pharmacology, Ajou University School of Medicine, Suwon, Republic of KoreaABSTRACTAn 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.https://www.tandfonline.com/doi/10.1080/19768354.2022.2158219Actin depolymerizationF-actin-binding proteinsLeucine-rich repeat serine-threonine protein kinase-2Parkinson disease 8microglia
spellingShingle Beomsue Kim
Young Ho Suh
Eunhye Joe
LRRK2 decreases microglial actin dynamics by filamentous actin depolymerization and Rac1 inhibition
Animal Cells and Systems
Actin depolymerization
F-actin-binding proteins
Leucine-rich repeat serine-threonine protein kinase-2
Parkinson disease 8
microglia
title LRRK2 decreases microglial actin dynamics by filamentous actin depolymerization and Rac1 inhibition
title_full LRRK2 decreases microglial actin dynamics by filamentous actin depolymerization and Rac1 inhibition
title_fullStr LRRK2 decreases microglial actin dynamics by filamentous actin depolymerization and Rac1 inhibition
title_full_unstemmed LRRK2 decreases microglial actin dynamics by filamentous actin depolymerization and Rac1 inhibition
title_short LRRK2 decreases microglial actin dynamics by filamentous actin depolymerization and Rac1 inhibition
title_sort lrrk2 decreases microglial actin dynamics by filamentous actin depolymerization and rac1 inhibition
topic Actin depolymerization
F-actin-binding proteins
Leucine-rich repeat serine-threonine protein kinase-2
Parkinson disease 8
microglia
url https://www.tandfonline.com/doi/10.1080/19768354.2022.2158219
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AT eunhyejoe lrrk2decreasesmicroglialactindynamicsbyfilamentousactindepolymerizationandrac1inhibition