Directors' Research Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Institute of Genetics, University of Cologne, 50674 Cologne, Germany.
Proc Natl Acad Sci U S A. 2017 Nov 28;114(48):E10389-E10398. doi: 10.1073/pnas.1711408114. Epub 2017 Nov 14.
Tango1 enables ER-to-Golgi trafficking of large proteins. We show here that loss of Tango1, in addition to disrupting protein secretion and ER/Golgi morphology, causes ER stress and defects in cell shape. We find that the previously observed dependence of smaller cargos on Tango1 is a secondary effect. If large cargos like Dumpy, which we identify as a Tango1 cargo, are removed from the cell, nonbulky proteins reenter the secretory pathway. Removal of blocking cargo also restores cell morphology and attenuates the ER-stress response. Thus, failures in the secretion of nonbulky proteins, ER stress, and defective cell morphology are secondary consequences of bulky cargo retention. By contrast, ER/Golgi defects in Tango1-depleted cells persist in the absence of bulky cargo, showing that they are due to a secretion-independent function of Tango1. Therefore, maintenance of ER/Golgi architecture and bulky cargo transport are the primary functions for Tango1.
Tango1 促进内质网到高尔基体的大蛋白运输。我们在这里发现，除了破坏蛋白质分泌和内质网/高尔基体形态外，Tango1 的缺失还会导致内质网应激和细胞形态缺陷。我们发现，以前观察到的较小货物对 Tango1 的依赖性是一种次要效应。如果像 Dumpy 这样的大货物（我们确定为 Tango1 的货物）从细胞中去除，非大量的蛋白质会重新进入分泌途径。去除阻塞货物也会恢复细胞形态并减轻内质网应激反应。因此，非大量蛋白质分泌失败、内质网应激和细胞形态缺陷是大量货物保留的次要后果。相比之下，在没有大量货物的情况下，Tango1 耗尽细胞中的内质网/高尔基体缺陷仍然存在，表明它们是由于 Tango1 的一种与分泌无关的功能。因此，维持内质网/高尔基体结构和大货物运输是 Tango1 的主要功能。
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