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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Format: | Article |
Language: | English |
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Taylor & Francis Group
2022-11-01
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Series: | Animal Cells and Systems |
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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. |
first_indexed | 2024-03-13T08:22:45Z |
format | Article |
id | doaj.art-8141f10e750f4c7197cacb75f9e61cdb |
institution | Directory Open Access Journal |
issn | 1976-8354 2151-2485 |
language | English |
last_indexed | 2024-03-13T08:22:45Z |
publishDate | 2022-11-01 |
publisher | Taylor & Francis Group |
record_format | Article |
series | Animal Cells and Systems |
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 |
work_keys_str_mv | AT beomsuekim lrrk2decreasesmicroglialactindynamicsbyfilamentousactindepolymerizationandrac1inhibition AT younghosuh lrrk2decreasesmicroglialactindynamicsbyfilamentousactindepolymerizationandrac1inhibition AT eunhyejoe lrrk2decreasesmicroglialactindynamicsbyfilamentousactindepolymerizationandrac1inhibition |