Institute of Molecular Medicine, Taipei, Taiwan.
Institute of Molecular Medicine, Taipei, Taiwan; Center of Precision Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Cell Rep. 2022 Mar 22;38(12):110488. doi: 10.1016/j.celrep.2022.110488.
The accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR), which acts through various mechanisms to reduce ER stress. While the UPR has been well studied for its effects on the ER, its impact on the Golgi is less understood. The Golgi complex receives transport vesicles from the endosome through two types of tethering factors: long coiled-coil golgin and the multisubunit Golgi-associated retrograde protein (GARP) complex. Here, we report that ER stress increases the phosphorylation of golgin Imh1 to maintain the GARP-mediated recycling of the SNAREs Snc1 and Tlg1. We also identify a specific function of the Golgi affected by ER stress and elucidate a homeostatic response to restore this function, which involves both an Ire1-dependent and a MAP kinase Slt2/ERK2-dependent mechanism. Furthermore, our findings advance a general understanding of how two different types of tethers act cooperatively to mediate a transport pathway.
内质网（ER）中错误折叠蛋白的积累会诱导未折叠蛋白反应（UPR），该反应通过多种机制来减轻 ER 应激。虽然 UPR 对 ER 的影响已经得到了很好的研究，但它对高尔基体的影响却知之甚少。高尔基体复合物通过两种类型的 tethering factors（长卷曲螺旋高尔基体和多亚基高尔基体相关逆行蛋白（GARP）复合物）从内体接收运输小泡。在这里，我们报告 ER 应激会增加 golgin Imh1 的磷酸化，以维持 GARP 介导的 SNAREs Snc1 和 Tlg1 的回收。我们还确定了一个受 ER 应激影响的高尔基体的特定功能，并阐明了一种恢复此功能的体内平衡反应，该反应涉及 Ire1 依赖性和 MAP 激酶 Slt2/ERK2 依赖性机制。此外，我们的发现提高了对两种不同类型的 tether 如何协同作用来介导运输途径的一般理解。
