Abstract：
TANGO1, TANGO1-Short, and cTAGE5 form stable complexes at the endoplasmic reticulum exit sites (ERES) to preferably export bulky cargoes. Their C-terminal proline-rich domain (PRD) binds Sec23A and affects COPII assembly. The PRD in TANGO1-Short was replaced with light-responsive domains to control its binding to Sec23A in U2OS cells (human osteosarcoma). TANGO1-ShortΔPRD was dispersed in the ER membrane but relocated rapidly, reversibly, to pre-existing ERES by binding to Sec23A upon light activation. Prolonged binding between the two, concentrated ERES in the juxtanuclear region, blocked cargo export and relocated ERGIC53 into the ER, minimally impacting the Golgi complex organization. Bulky collagen VII and endogenous collagen I were collected at less than 47% of the stalled ERES, whereas small cargo molecules were retained uniformly at almost all the ERES. We suggest that ERES are segregated to handle cargoes based on their size, permitting cells to traffic them simultaneously for optimal secretion.
摘要：
TANGO1,TANGO1-短,和cTAGE5在内质网出口位点(ERES)处形成稳定的复合物,以优选地输出大体积的货物。它们的C端富含脯氨酸的结构域(PRD)结合Sec23A并影响COPII组装。TANGO1-Short中的PRD用光响应域代替，以控制其与U2OS细胞（人骨肉瘤）中Sec23A的结合。TANGO1-ShortΔPRD分散在ER膜中，但迅速重新定位，可逆地，通过在光激活时与Sec23A结合，以预先存在的ERES。两者之间的长期结合，在近核区域集中的ERES，封锁了货物出口，并将ERGIC53转移到急诊室，对高尔基复合体组织的影响最小。大量的胶原蛋白VII和内源性胶原蛋白I在低于47％的停滞的ERES收集，而小货物分子在几乎所有的ERES上都均匀保留。我们建议ERES根据货物的大小进行隔离处理，允许细胞同时运输它们以获得最佳分泌。
