Cells are constantly exposed to various chemical and physical stimuli. While much has been learned about the biochemical factors that regulate secretory trafficking from the endoplasmic reticulum (ER), much less is known about whether and how this trafficking is subject to regulation by mechanical signals. Here, we show that subjecting cells to mechanical strain both induces the formation of ER exit sites (ERES) and accelerates ER-to-Golgi trafficking. We found that cells with impaired ERES function were less capable of expanding their surface area when placed under mechanical stress and were more prone to develop plasma membrane defects when subjected to stretching. Thus, coupling of ERES function to mechanotransduction appears to confer resistance of cells to mechanical stress. Furthermore, we show that the coupling of mechanotransduction to ERES formation was mediated via a previously unappreciated ER-localized pool of the small GTPase Rac1. Mechanistically, we show that Rac1 interacts with the small GTPase Sar1 to drive budding of COPII carriers and stimulates ER-to-Golgi transport. This interaction therefore represents an unprecedented link between mechanical strain and export from the ER.

中文翻译：

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机械应变通过 Rac1 刺激 COPII 依赖性分泌物运输


细胞不断暴露于各种化学和物理刺激。虽然人们对调节内质网（ER）分泌性运输的生化因素了解很多，但对于这种运输是否以及如何受到机械信号的调节却知之甚少。在这里，我们表明，使细胞受到机械应变既能诱导内质网出口位点（ERES）的形成，又能加速内质网到高尔基体的运输。我们发现，ERES 功能受损的细胞在受到机械应力时扩展表面积的能力较差，并且在受到拉伸时更容易出现质膜缺陷。因此，ERES 功能与机械转导的耦合似乎赋予细胞对机械应力的抵抗力。此外，我们还发现，机械转导与 ERES 形成的耦合是通过先前未被重视的小 GTPase Rac1 的 ER 定位库介导的。从机制上讲，我们表明 Rac1 与小 GTPase Sar1 相互作用，驱动 COPII 载体的出芽并刺激 ER 到高尔基体的运输。因此，这种相互作用代表了机械应变和内质网输出之间前所未有的联系。