DIAPH3 condensates formed by liquid-liquid phase separation act as a regulatory hub for stress-induced actin cytoskeleton remodeling
Summary: 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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124722018903 |
| _version_ | 1828066629001412608 |
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| author | Ke Zhang Miaodan Huang Ang Li Jing Wen Lingli Yan Yunhao Li Liman Guo Kumaran Satyanarayanan Senthil Yangyang Zhou Guobing Chen Yong Liu Xiaofei Zhang Xiaoli Yao Dajiang Qin Huanxing Su |
| author_facet | Ke Zhang Miaodan Huang Ang Li Jing Wen Lingli Yan Yunhao Li Liman Guo Kumaran Satyanarayanan Senthil Yangyang Zhou Guobing Chen Yong Liu Xiaofei Zhang Xiaoli Yao Dajiang Qin Huanxing Su |
| author_sort | Ke Zhang |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-10T23:33:16Z |
| format | Article |
| id | doaj.art-c79dbece46364d8da5c29adff26dcd35 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-10T23:33:16Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c79dbece46364d8da5c29adff26dcd352023-01-12T04:18:59ZengElsevierCell Reports2211-12472023-01-01421111986DIAPH3 condensates formed by liquid-liquid phase separation act as a regulatory hub for stress-induced actin cytoskeleton remodelingKe Zhang0Miaodan Huang1Ang Li2Jing Wen3Lingli Yan4Yunhao Li5Liman Guo6Kumaran Satyanarayanan Senthil7Yangyang Zhou8Guobing Chen9Yong Liu10Xiaofei Zhang11Xiaoli Yao12Dajiang Qin13Huanxing Su14State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaGuangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaInstitute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, ChinaLaboratory of Neuroscience in Health and Disease Institute, Guangzhou First People’s Hospital School of Medicine, South China University of Technology, Guangzhou, ChinaGuangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaDepartment of Neurology, National Key Clinical Department and Key Discipline of Neurology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaKey Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124722018903CP: Cell biology |
| spellingShingle | Ke Zhang Miaodan Huang Ang Li Jing Wen Lingli Yan Yunhao Li Liman Guo Kumaran Satyanarayanan Senthil Yangyang Zhou Guobing Chen Yong Liu Xiaofei Zhang Xiaoli Yao Dajiang Qin Huanxing Su DIAPH3 condensates formed by liquid-liquid phase separation act as a regulatory hub for stress-induced actin cytoskeleton remodeling Cell Reports CP: Cell biology |
| title | DIAPH3 condensates formed by liquid-liquid phase separation act as a regulatory hub for stress-induced actin cytoskeleton remodeling |
| title_full | DIAPH3 condensates formed by liquid-liquid phase separation act as a regulatory hub for stress-induced actin cytoskeleton remodeling |
| title_fullStr | DIAPH3 condensates formed by liquid-liquid phase separation act as a regulatory hub for stress-induced actin cytoskeleton remodeling |
| title_full_unstemmed | DIAPH3 condensates formed by liquid-liquid phase separation act as a regulatory hub for stress-induced actin cytoskeleton remodeling |
| title_short | DIAPH3 condensates formed by liquid-liquid phase separation act as a regulatory hub for stress-induced actin cytoskeleton remodeling |
| title_sort | diaph3 condensates formed by liquid liquid phase separation act as a regulatory hub for stress induced actin cytoskeleton remodeling |
| topic | CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124722018903 |
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