Artlett Carol M, Connolly Lianne M
Drexel University College of Medicine, Drexel University, Philadelphia, PA 19129, USA.
Fibrosis (Hong Kong). 2023 Dec;1(2). doi: 10.35534/fibrosis.2023.10008. Epub 2023 Dec 21.
The endoplasmic reticulum (ER) to Golgi secretory pathway is an elegantly complex process whereby protein cargoes are manufactured, folded, and distributed from the ER to the cisternal layers of the Golgi stack before they are delivered to their final destinations. The export of large bulky cargoes such as procollagen and its trafficking to the Golgi is a sophisticated mechanism requiring TANGO1 (Transport ANd Golgi Organization protein 1. It is also called MIA3 (Melanoma Inhibitory Activity protein 3). TANGO1 has two prominent isoforms, TANGO1-Long and TANGO1-Short, and each isoform has specific functions. On the luminal side, TANGO1-Long has an HSP47 recruitment domain and uses this protein to collect collagen. It can also tether its paralog isoforms cTAGE5 and TALI and along with these proteins enlarges the vesicle to accommodate procollagen. Recent studies show that TANGO1-Long combines retrograde membrane flow with anterograde cargo transport. This complex mechanism is highly activated in fibrosis and promotes the excessive deposition of collagen in the tissues. The therapeutic targeting of TANGO1 may prove successful in the control of fibrotic disorders. This review focuses on TANGO1 and its complex interaction with other procollagen export factors that modulate increased vesicle size to accommodate the export of procollagen.
内质网（ER）到高尔基体的分泌途径是一个极其复杂的过程，在此过程中，蛋白质货物在被输送到最终目的地之前，先在内质网中制造、折叠，然后从内质网运输到高尔基体堆叠的各层扁平囊泡中。诸如前胶原之类的大分子货物的输出及其向高尔基体的运输是一种复杂的机制，需要运输和高尔基体组织蛋白1（TANGO1）。它也被称为黑色素瘤抑制活性蛋白3（MIA3）。TANGO1有两种主要的异构体，即长TANGO1和短TANGO1，每种异构体都有特定的功能。在腔面，长TANGO1有一个热休克蛋白47（HSP47）募集结构域，并利用该蛋白收集胶原蛋白。它还可以连接其旁系异构体cTAGE5和TALI，并与这些蛋白一起扩大囊泡以容纳前胶原。最近的研究表明，长TANGO1将逆行膜流与顺行货物运输结合在一起。这种复杂的机制在纤维化过程中被高度激活，并促进胶原蛋白在组织中的过度沉积。TANGO1的治疗性靶向可能在控制纤维化疾病方面取得成功。本综述重点关注TANGO1及其与其他前胶原输出因子的复杂相互作用，这些因子调节囊泡大小增加以适应前胶原的输出。
