Maeda Miharu, Katada Toshiaki, Saito Kota
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan
J Cell Biol. 2017 Jun 5;216(6):1731-1743. doi: 10.1083/jcb.201703084. Epub 2017 Apr 25.
Mammalian endoplasmic reticulum (ER) exit sites export a variety of cargo molecules including oversized cargoes such as collagens. However, the mechanisms of their assembly and organization are not fully understood. TANGO1L is characterized as a collagen receptor, but the function of TANGO1S remains to be investigated. Here, we show that direct interaction between both isoforms of TANGO1 and Sec16 is not only important for their correct localization but also critical for the organization of ER exit sites. The depletion of TANGO1 disassembles COPII components as well as membrane-bound ER-resident complexes, resulting in fewer functional ER exit sites and delayed secretion. The ectopically expressed TANGO1 C-terminal domain responsible for Sec16 binding in mitochondria is capable of recruiting Sec16 and other COPII components. Moreover, TANGO1 recruits membrane-bound macromolecular complexes consisting of cTAGE5 and Sec12 to the ER exit sites. These data suggest that mammalian ER exit sites are organized by TANGO1 acting as a scaffold, in cooperation with Sec16 for efficient secretion.
哺乳动物内质网（ER）出口位点输出多种货物分子，包括诸如胶原蛋白等超大货物。然而，它们的组装和组织机制尚未完全了解。TANGO1L被表征为一种胶原蛋白受体，但TANGO1S的功能仍有待研究。在这里，我们表明TANGO1的两种同工型与Sec16之间的直接相互作用不仅对它们的正确定位很重要，而且对ER出口位点的组织也至关重要。TANGO1的缺失会拆解COPII组件以及膜结合的内质网驻留复合物，导致功能性ER出口位点减少和分泌延迟。在线粒体中负责与Sec16结合的异位表达的TANGO1 C末端结构域能够募集Sec16和其他COPII组件。此外，TANGO1将由cTAGE5和Sec12组成的膜结合大分子复合物募集到ER出口位点。这些数据表明，哺乳动物ER出口位点是由TANGO1作为支架组织起来的，与Sec16协同作用以实现高效分泌。
