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.

细胞通过未折叠蛋白反应 (UPR) 减轻内质网应激。在这里，我们报告了 ER 螺纹的形成作为 ER 应激反应的效应机制。我们发现强烈的内质网应激会诱导内质网螺旋的形成，其中包含内质网驻留蛋白，如 Sec61 复合物和 PKR 样 ER 激酶 (PERK)。ER 螺纹的形成依赖于 PERK 激酶活性，并由 COPII 机制介导，这有助于 ER 膜出芽形成管状囊泡 ER 螺纹前体。ER 螺纹前体然后通过 Sec22b 介导的融合形成 ER 螺纹。我们进一步表明，内质网螺纹可能通过调节 PERK 活性和在无核糖体的环境中隔离转位子，从而促进内质网应激诱导的翻译抑制。