Mechanism of large protein secretion regulated by small GTPase and complex localized at the ER

在ER中合成的胶原蛋白太大而不能装入常规的转运COPII载体。胶原蛋白如何从ER输出仍不清楚。我们以前已经确定cTAGE 5/TANGO 1复合物作为ER出口部位的VII型胶原的货物受体。在这里，我们表明，cTAGE 5相互作用与Sec 12，一个鸟嘌呤核苷酸交换因子Sar 1在ER出口网站。在cTAGE 5耗尽后，Sec 12从ER出口位点离域。这些结果表明，ER分泌的VII型胶原不仅受cTAGE 5/TANGO 1复合物的调节，而且还受Sar 1小GT3活性的调节。

Collagen synthesized in the ER is too big to fit into conventional transport COPII carriers. How collagen exports from the ER is still unclear. We have previously identified cTAGE5/TANGO1 complex as a cargo receptor for collagen VII at ER exit sites. Here we show that cTAGE5 interacts with Sec12, a guanine-nucleotide exchange factor of Sar1 at ER exit sites. Upon cTAGE5 depletion, Sec12 delocalizes from the ER exit sites. These results imply that collagen VII secretion from the ER is regulated not only by cTAGE5/TANGO1 complex but with the activity of Sar1 small GTPase.