TANGO1 recruits Sec16 to coordinately organize ER exit sites for efficient secretion.
TANGO1 recruits Sec16 to coordinately organize ER exit sites for efficient secretion.
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DOI：
10.1083/jcb.201703084
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发表时间：
2017-06-05
期刊：
影响因子：
--
通讯作者：
Saito K
中科院分区：
文献类型：
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作者：
Maeda M;Katada T;Saito K
哺乳动物内质网出口位点（ERES）输出各种货物分子，包括超大货物，如胶原蛋白。Maeda等人报道了TANGO 1和Sec 16在ERES中的直接相互作用，这不仅对它们的正确定位很重要，而且对ERES的组织也很关键。哺乳动物内质网（ER）出口位点输出各种货物分子，包括过大的货物，如胶原蛋白。然而，其组装和组织的机制尚未完全了解。TANGO 1 L是一种胶原蛋白受体，但TANGO 1 S的功能仍有待研究。在这里，我们表明，TANGO 1和Sec 16的两种亚型之间的直接相互作用不仅是重要的，他们的正确定位，但也是至关重要的组织ER出口网站。TANGO 1的耗竭分解COPII组分以及膜结合的ER驻留复合物，导致功能性ER退出位点减少和分泌延迟。异位表达的TANGO 1 C-末端结构域负责Sec 16在线粒体中的结合，能够募集Sec 16和其他COPII组分。此外，TANGO 1募集由cTAGE 5和Sec 12组成的膜结合大分子复合物到ER出口位点。这些数据表明，哺乳动物ER出口位点是由TANGO 1作为支架组织的，与Sec 16合作进行有效分泌。
Mammalian ER exit sites (ERES) export a variety of cargo molecules, including oversized cargoes such as collagens. Maeda et al. report a direct interaction between TANGO1 and Sec16 at ERES, which is not only important for their correct localization but also critical for the organization of ERES. 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.