Saito Kota, Yamashiro Koh, Shimazu Noriko, Tanabe Tomoya, Kontani Kenji, Katada Toshiaki
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Cell Biol. 2014 Sep 15;206(6):751-62. doi: 10.1083/jcb.201312062. Epub 2014 Sep 8.
Mechanisms for exporting variably sized cargo from the endoplasmic reticulum (ER) using the same machinery remain poorly understood. COPII-coated vesicles, which transport secretory proteins from the ER to the Golgi apparatus, are typically 60-90 nm in diameter. However, collagen, which forms a trimeric structure that is too large to be accommodated by conventional transport vesicles, is also known to be secreted via a COPII-dependent process. In this paper, we show that Sec12, a guanine-nucleotide exchange factor for Sar1 guanosine triphosphatase, is concentrated at ER exit sites and that this concentration of Sec12 is specifically required for the secretion of collagen VII but not other proteins. Furthermore, Sec12 recruitment to ER exit sites is organized by its direct interaction with cTAGE5, a previously characterized collagen cargo receptor component, which functions together with TANGO1 at ER exit sites. These findings suggest that the export of large cargo requires high levels of guanosine triphosphate-bound Sar1 generated by Sec12 localized at ER exit sites.
利用相同机制从内质网（ER）输出大小各异的货物的机制仍知之甚少。COPII包被囊泡负责将分泌蛋白从内质网运输到高尔基体，其直径通常为60 - 90纳米。然而，胶原蛋白形成的三聚体结构太大，无法被传统运输囊泡容纳，但已知它也是通过COPII依赖的过程分泌的。在本文中，我们表明，Sec12，一种Sar1鸟苷三磷酸酶的鸟嘌呤核苷酸交换因子，集中在内质网出口位点，并且这种Sec12的集中对于VII型胶原蛋白的分泌是特别必需的，而对其他蛋白质则不是。此外，Sec12被招募到内质网出口位点是由其与cTAGE5的直接相互作用所组织的，cTAGE5是一种先前已被表征的胶原蛋白货物受体成分，它在内质网出口位点与TANGO1共同发挥作用。这些发现表明，大型货物的输出需要由位于内质网出口位点的Sec12产生的高水平鸟苷三磷酸结合的Sar1。
