title: Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators.
abstract: 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.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom. karl.kadler@manchester.ac.uk
authors.forename: Karl E
authors.initials: KE
authors.lastname: Kadler
authors.forename: Adele
authors.initials: A
authors.lastname: Hill
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Canty-Laird
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008958:Models, Molecular; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D016023:Integrins; D020033:Protein Isoforms; D003094:Collagen