Kadler Karl E, Hill Adele, Canty-Laird Elizabeth G
Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom.
Curr Opin Cell Biol. 2008 Oct;20(5):495-501. doi: 10.1016/j.ceb.2008.06.008. Epub 2008 Jul 30.
Collagens are triple helical proteins that occur in the extracellular matrix (ECM) and at the cell-ECM interface. There are more than 30 collagens and collagen-related proteins but the most abundant are collagens I and II that exist as D-periodic (where D = 67 nm) fibrils. The fibrils are of broad biomedical importance and have central roles in embryogenesis, arthritis, tissue repair, fibrosis, tumor invasion, and cardiovascular disease. Collagens I and II spontaneously form fibrils in vitro, which shows that collagen fibrillogenesis is a selfassembly process. However, the situation in vivo is not that simple; collagen I-containing fibrils do not form in the absence of fibronectin, fibronectin-binding and collagen-binding integrins, and collagen V. Likewise, the thin collagen II-containing fibrils in cartilage do not form in the absence of collagen XI. Thus, in vivo, cellular mechanisms are in place to control what is otherwise a protein self-assembly process. This review puts forward a working hypothesis for how fibronectin and integrins (the organizers) determine the site of fibril assembly, and collagens V and XI (the nucleators) initiate collagen fibrillogenesis.
胶原蛋白是存在于细胞外基质（ECM）以及细胞与ECM界面的三螺旋蛋白。胶原蛋白及与胶原蛋白相关的蛋白有30多种，但最丰富的是I型和II型胶原蛋白，它们以D周期（D = 67纳米）的原纤维形式存在。这些原纤维具有广泛的生物医学重要性，在胚胎发育、关节炎、组织修复、纤维化、肿瘤侵袭和心血管疾病中发挥着核心作用。I型和II型胶原蛋白在体外能自发形成原纤维，这表明胶原蛋白原纤维形成是一个自组装过程。然而，体内情况并非如此简单；在没有纤连蛋白、纤连蛋白结合和胶原蛋白结合整合素以及V型胶原蛋白的情况下，含I型胶原蛋白的原纤维无法形成。同样，在没有XI型胶原蛋白的情况下，软骨中含II型胶原蛋白的细原纤维也无法形成。因此，在体内，细胞机制会对原本是蛋白质自组装的过程进行调控。本综述提出了一个工作假说，即纤连蛋白和整合素（组织者）如何决定原纤维组装的位点，以及V型和XI型胶原蛋白（成核剂）如何启动胶原蛋白原纤维形成。
