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DIAPH3 condensates formed by liquid-liquid phase separation act as a regulatory hub for stress-induced actin cytoskeleton remodeling

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机构: [1]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China [2]Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China [3]Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China [4]Laboratory of Neuroscience in Health and Disease Institute, Guangzhou First People’s Hospital School of Medicine, South China University of Technology, Guangzhou, China [5]Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China [6]Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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Membraneless condensates, such as stress granules (SGs) and processing bodies (P-bodies), have attracted wide attention due to their unique feature of rapid response to stress without first requiring nuclear feedback. In this study, we identify diaphanous-related formin 3 (DIAPH3), an actin nucleator, as a scaffold protein to initiate liquid-liquid phase separation (LLPS) and form abundant cytosolic phase-separated DIAPH3 granules (D-granules) in mammalian cells such as HeLa, HEK293, and fibroblasts under various stress conditions. Neither mRNAs nor known stress-associated condensate markers, such as G3BP1, G3BP2, and TIA1 for SGs and DCP1A for P-bodies, are detected in D-granules. Using overexpression and knockout of DIAPH3, pharmacological interventions, and optogenetics, we further demonstrate that stress-induced D-granules spatially sequester DIAPH3 within the condensation to inhibit the assembly of actin filaments in filopodia. This study reveals that D-granules formed by LLPS act as a regulatory hub for actin cytoskeletal remodeling in response to stress.Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

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大类 | 1 区 生物学
小类 | 2 区 细胞生物学
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大类 | 1 区 生物学
小类 | 2 区 细胞生物学
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Q1 CELL BIOLOGY
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Q1 CELL BIOLOGY

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第一作者机构: [1]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
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