Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1085.
Department of Neurology, University of Michigan School of Medicine, Ann Arbor, MI 48109-1085.
Mol Biol Cell. 2019 Mar 15;30(6):766-777. doi: 10.1091/mbc.E18-07-0462. Epub 2019 Jan 16.
The Golgi apparatus is a membrane-bound organelle that serves as the center for trafficking and processing of proteins and lipids. To perform these functions, the Golgi forms a multilayer stacked structure held by GRASP55 and GRASP65 trans-oligomers and perhaps their binding partners. Depletion of GRASP proteins disrupts Golgi stack formation and impairs critical functions of the Golgi, such as accurate protein glycosylation and sorting. However, how Golgi destruction affects other cellular activities is so far unknown. Here, we report that depletion of GRASP proteins reduces cell attachment and migration. Interestingly, GRASP depletion reduces the protein level of α5β1 integrin, the major cell adhesion molecule at the surface of HeLa and MDA-MB-231 cells, due to decreased integrin protein synthesis. GRASP depletion also increases cell growth and total protein synthesis. These new findings enrich our understanding on the role of the Golgi in cell physiology and provide a potential target for treating protein-trafficking disorders.
高尔基器是一种膜结合细胞器，作为蛋白质和脂质运输和加工的中心。为了执行这些功能，高尔基器形成一个多层堆叠的结构，由 GRASP55 和 GRASP65 跨寡聚物以及它们的结合伴侣支撑。GRASP 蛋白的耗竭会破坏高尔基堆栈的形成，并损害高尔基器的关键功能，如蛋白质的糖基化和分拣的准确性。然而，高尔基器的破坏如何影响其他细胞活动目前尚不清楚。在这里，我们报告说，GRASP 蛋白的耗竭会降低细胞的附着和迁移。有趣的是，由于整合素蛋白合成减少，GRASP 耗竭会降低 HeLa 和 MDA-MB-231 细胞表面的主要细胞黏附分子α5β1 整联蛋白的蛋白水平。GRASP 耗竭还会增加细胞生长和总蛋白合成。这些新发现丰富了我们对高尔基器在细胞生理学中的作用的理解，并为治疗蛋白质运输障碍提供了一个潜在的靶点。
