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作 者:Xuezhao Feng Wanqing Du Mingrui Ding Wenkang Zhao Xirenayi Xirefu Meisheng Ma Yuhui Zhuang Xiaoyu Fu Jiangfeng Shen Jinpei Zhang Xiuying Lei Daxiao Sun Qing Xi Yiliyasi Aisa Qian Chenr Ying Li Wenjuan Wang Shanjin Huang Li Yu Pilong Li Na Mi
机构地区:[1]State Key Laboratory of Pathogenesis,Prevention and Treatment of Central Asian High Incidence Diseases,Clinical Medical Research Institute,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang,China [2]Basic Medical College,Xinjiang Medical University,Urumqi,Xinjiang,China [3]State Key Laboratory of Membrane Biology,Tsinghua University-Peking University Joint Center for Life Sciences,School of Life Sciences,Tsinghua University,Beijing,China [4]Beijing Advanced Innovation Center for Structural Biology&Frontier Research Center for Biological Structure,Tsinghua University-Peking University Joint Center for Life Sciences,School of Life Sciences,Tsinghua University,Beijing,China [5]College of Pharmacy,Xinjiang Medical University,Urumqi,Xinjiang,China [6]Rongji Medical College of Huazhong University of Science and Technology,Wuhan,Hubei,China [7]Center for Plant Biology,School of Life Sciences,Tsinghua University,Beijing,China [8]Ministry of Education Key Laboratory of Protein Sciences,Beijing Advanced Innovation Center for Structural Biology,Beijing Frontier Research Center of Biological Structures,School of Life Sciences,Tsinghua University,Beijing,China [9]Center of Biomedical Analysis,Tsinghua University,Beijing,China
出 处:《Cell Research》2022年第7期659-669,共11页细胞研究(英文版)
基 金:supported by the Ministry of Science and Technology of China(2017YFA0506300 to N.M.;2019YFA0508403 to P.L.);the National Natural Science Foundation of China(31771536,31860316).
摘 要:Biomolecular condensation driven by liquid-liquid phase separation(LLPS)is key to assembly of membraneless organelles in numerous crucial pathways.It is largely unknown how cellular structures or components spatiotemporally regulate LLPS and condensate formation.Here we reveal that cytoskeletal dynamics can control the condensation of p62 bodies comprising the autophagic adaptor p62/SQSTM1 and poly-ubiquitinated cargos.Branched actin networks are associated with p62 bodies and are required for their conden satio n.Myosi n 1D,a bran ched acti n-associated motor protein,drives coalesce nee of small nano scale p62 bodies into large micron-scale condensates along the branched actin network.Impairment of actin cytoskeletal networks compromises the condensation of p62 bodies and retards substrate degradation by autophagy in both cellular models and Myosin ID knockout mice.Coupling of LLPS scaffold to cytoskeleton systems may represent a general mechanism by which cells exert spatiotemporal control over phase condensation processes.
关 键 词:CONDENSATION P62 network
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