Volume 31, No 2, Feb 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 2, February 2021: 141-156   |  Open Access

ORIGINAL ARTICLES

COPII mitigates ER stress by promoting formation of ER whorls

Fang Xu¹ , Wanqing Du¹ , Qin Zou² , Yuting Wang² , Xin Zhang¹ , Xudong Xing² , Ying Li¹ , Dachuan Zhang¹ , Huimin Wang³ , Wenhao Zhang¹ , Xinyao Hu⁴ , Xin Liu¹ , Xiaoling Liu¹ , Shaojin Zhang¹ , Jinqiang Yu¹ , Jianhuo Fang² , Fajin Li² , Ying Zhou⁵ , Tieqiang Yue⁵ , Na Mi⁶ , Haiteng Deng² , Peng Zou^5,7 , Xiaowei Chen^3,8,9 , Xuerui Yang^2,* , Li Yu^1,*

¹The 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
²MOE Key Laboratory of Bioinformatics, Center for Synthetic & Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
³Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China
⁴National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
⁵College 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
⁶Xinjiang Medical University, Urumqi, Xinjiang 830011, China
⁷Chinese Institute for Brain Research (CIBR), Beijing 102206, China
⁸State Key Laboratory of Membrane Biology, Peking University, Beijing 100871, China
⁹Institute of Molecular Medicine, Peking University, Beijing 100871, China
These authors contributed equally: Fang Xu, Wanqing Du, Qin Zou, Yuting Wang Correspondence: Xuerui Yang(yangxuerui@tsinghua.edu.cn)Li Yu(liyulab@mail.tsinghua.edu.cn)

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 stress-induced 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.

https://doi.org/10.1038/s41422-020-00416-2

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