TANGO1、TANGO1-Short 和 cTAGE5 在内质网出口位点 (ERES) 形成稳定的复合物，以更好地输出大体积货物。它们的 C 端富含脯氨酸结构域 (PRD) 结合 Sec23A 并影响 COPII 组装。 TANGO1-Short 中的 PRD 被光响应结构域取代，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，但在光激活后通过与 Sec23A 结合，快速、可逆地重新定位到预先存在的 ERES。两者之间的长时间结合，使 ERES 集中在核旁区域，阻碍了货物输出并将 ERGIC53 重新定位到 ER 中，从而对高尔基复合体组织的影响最小化。大体积胶原蛋白 VII 和内源性胶原蛋白 I 在不到 47% 的停滞 ERES 处被收集，而小货物分子则在几乎所有 ERES 处被均匀保留。我们建议根据货物的大小将 ERES 分开来处理货物，从而允许细胞同时运输货物以实现最佳分泌。版权所有 © 2024 Elsevier Inc. 保留所有权利。

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.Copyright © 2024 Elsevier Inc. All rights reserved.