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作 者:Fang Xu Wanqing Du Qin Zou Yuting Wang Xin Zhang Xudong Xing Ying Li Dachuan Zhang Huimin Wang Wenhao Zhang Xinyao Hu Xin Liu Xiaoling Liu Shaojin Zhang Jinqiang Yu Jianhuo Fang Fajin Li Ying Zhou Tieqiang Yue Na Mi Haiteng Deng Peng Zou Xiaowei Chen Xuerui Yang Li Yu
机构地区:[1]The State Key Laboratory of Membrane Biology,Tsinghua University-Peking University Joint Centre for Life Sciences,Beijing Frontier Research Center for Biological Structure,School of Life Sciences,Tsinghua University,Beijing 100084,China [2]MOE Key Laboratory of Bioinformatics,Center for Synthetic&Systems Biology,School of Life Sciences,Tsinghua University,Beijing 100084,China [3]Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China [4]National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [5]College of Chemistry and Molecular Engineering,Synthetic and Functional Biomolecules Center,Beijing National Laboratory for Molecular Sciences,Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,PKU-IDG/McGovern Institute for Brain Research,Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China [6]Xinjiang Medical University,Urumqi,Xinjiang 830011,China [7]Chinese Institute for Brain Research(CIBR),Beijing 102206,China [8]State Key Laboratory of Membrane Biology,Peking University,Beijing 100871,China [9]Institute of Molecular Medicine,Peking University,Beijing 100871,China
出 处:《Cell Research》2021年第2期141-156,共16页细胞研究(英文版)
基 金:the Ministry of Science and Technology of China(2017YFA0503404 and 2016YFA0500202);L.Y.,the National Natural Science Foundation of China(31790401);the Natural Science Foundation of China international cooperation and exchange program(31561143002);the Independent Research of Tsinghua University(20161080135)to L.Y.
摘 要:Cells mitigate ER stress through the unfolded protein response(UPR).Here,we report formation of ER whorls as an effector mechanism of the ER stress response.We found that strong ER stress induces formation of ER whorls,which contain ER-resident proteins such as the Sec61 complex and PKR-like ER kinase(PERK).ER whorl formation is dependent on PERK kinase activity and is mediated by COPII machinery,which facilitates ER membrane budding to form tubular-vesicular ER whorl precursors.ER whorl precursors then go through Sec22b-mediated fusion to form ER whorls.We further show that ER whorls contribute to ER stressinduced translational inhibition by possibly modulating PERK activity and by sequestering translocons in a ribosome-free environment.We propose that formation of ER whorls reflects a new type of ER stress response that controls inhibition of protein translation.
关 键 词:STRESS ). environment.
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