Annu Rev Cell Dev Biol. 2015;31:109-24. doi: 10.1146/annurev-cellbio-100913-013002. Epub 2015 Sep 29.
COPII vesicles mediate export of secretory cargo from the endoplasmic reticulum (ER). However, a standard COPII vesicle with a diameter of 60-90 nm is too small to export collagens that are composed of rigid triple helices of up to 400 nm in length. How do cells pack and secrete such bulky molecules? This issue is fundamentally important, as collagens constitute approximately 25% of our dry body weight and are essential for almost all cell-cell interactions. Recently, a potential mechanism for the biogenesis of mega-transport carriers was identified, involving packing collagens and increasing the size of COPII coats. Packing is mediated by TANGO1, which binds procollagen VII in the lumen and interacts with the COPII proteins Sec23/Sec24 on the cytoplasmic side of the ER. Cullin3, an E3 ligase, and its specific adaptor protein, KLHL12, ubiquitinate Sec31, which could increase the size of COPII coats. Recruitment of these proteins and their specific interactors into COPII-mediated vesicle biogenesis may be all that is needed for the export of bulky collagens from the ER. Nonetheless, we present an alternative pathway in which TANGO1 and COPII cooperate to export collagens without generating a mega-transport carrier.
COPII 小泡介导从内质网（ER）输出分泌性货物。然而，直径为 60-90nm 的标准 COPII 小泡太小，无法输出由长达 400nm 的刚性三螺旋组成的胶原。细胞如何包装和分泌如此庞大的分子？这个问题非常重要，因为胶原约占我们干体重的 25%，几乎对所有细胞间相互作用都是必不可少的。最近，一种用于巨型运输载体生物发生的潜在机制被确定，涉及包装胶原并增加 COPII 外套的尺寸。包装由 TANGO1 介导，TANGO1 在腔中结合前胶原 VII，并与内质网细胞质侧的 COPII 蛋白 Sec23/Sec24 相互作用。E3 连接酶 Cullin3 及其特定衔接蛋白 KLHL12 泛素化 Sec31，这可能会增加 COPII 外套的尺寸。这些蛋白质及其特定相互作用蛋白被招募到 COPII 介导的小泡生物发生中，可能是从 ER 输出庞大胶原所必需的。尽管如此，我们提出了一种替代途径，其中 TANGO1 和 COPII 合作，无需生成巨型运输载体即可输出胶原。
