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.
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COPII mitigates ER stress by promoting formation of ER whorls, Cell Res, 28 Sep 2020
Cell Research, 28 September, 2020, DOI：https://doi.org/10.1038/s41422-020-00416-2
COPII mitigates ER stress by promoting formation of ER whorls
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
Abstract
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.
文章链接：https://www.nature.com/articles/s41422-020-00416-2