Cell Biology Laboratories, School of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol, UK.
Wolfson Bioimaging Facility, Faculty of Biomedical Sciences, University of Bristol, Bristol, UK.
J Cell Biol. 2019 Mar 4;218(3):929-948. doi: 10.1083/jcb.201806035. Epub 2018 Dec 26.
Secretion and assembly of collagen are fundamental to the function of the extracellular matrix. Defects in the assembly of a collagen matrix lead to pathologies including fibrosis and osteogenesis imperfecta. Owing to the size of fibril-forming procollagen molecules it is assumed that they are transported from the endoplasmic reticulum to the Golgi in specialized large COPII-dependent carriers. Here, analyzing endogenous procollagen and a new engineered GFP-tagged form, we show that transport to the Golgi occurs in the absence of large (>350 nm) carriers. Large GFP-positive structures were observed occasionally, but these were nondynamic, are not COPII positive, and are labeled with markers of the ER. We propose a short-loop model of COPII-dependent ER-to-Golgi traffic that, while consistent with models of ERGIC-dependent expansion of COPII carriers, does not invoke long-range trafficking of large vesicular structures. Our findings provide an important insight into the process of procollagen trafficking and reveal a short-loop pathway from the ER to the Golgi, without the use of large carriers.
胶原蛋白的分泌和组装对细胞外基质的功能至关重要。胶原蛋白基质组装缺陷会导致纤维化和骨不全症等病变。由于纤维状原胶原蛋白分子的大小,人们假设它们是通过特殊的大 COPII 依赖性载体从内质网运输到高尔基体的。在这里,通过分析内源性原胶原蛋白和一种新的工程 GFP 标记形式,我们表明,在没有大(> 350nm)载体的情况下,原胶原蛋白向高尔基体的运输就会发生。偶尔会观察到大型 GFP 阳性结构,但这些结构是非动态的,不具有 COPII 阳性,并且被内质网的标记物标记。我们提出了一个 COPII 依赖性内质网到高尔基体运输的短环模型,虽然与 ERGIC 依赖性 COPII 载体扩展模型一致,但不涉及大囊泡结构的长距离运输。我们的研究结果为原胶原蛋白运输过程提供了重要的见解,并揭示了从内质网到高尔基体的短环途径,而无需使用大型载体。