Removal of fibrillar collagen N-propeptides
Species Homo sapiens
Fibrillar collagen is synthesized in the ER as procollagen with N- and C-terminal propeptides flanking the collagenous domain (Bellamy & Bornstein 1971). These propeptides, particularly the C-propeptide, inhibit fibril formation (Kadler et al. 1987). Propeptide removal and self-assembly of collagen into fibrils can be studied in vitro (Kadler et al. 1987). Early studies of propeptide processing identified enzymes in the medium of cultured cells (Kerwar et al. 1973, Layman & Ross 1973). The removal of propeptides is generally described as an extracellular process, but accumulating evidence suggests that fibril assembly can begin in the secretory pathway and at the plasma membrane (Canty & Kadler 2005). Procollagen processing in tendon fibroblasts was initiated within the secretory pathway, with the N-propetides removed first in the ER or an intermediate between the ER and Golgi. The C peptides were removed later, probably at the cell membrane-ECM interface (Canty-Laird et al. 2012).
Processing of procollagens I, II, and III results in an almost complete removal of both the N- and C-propeptides. Procollagen type I-III N-propeptides are removed by disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family members -2, -3 and 14*. These are themselves synthesized as proenzymes and activated by the removal of an inhibitory prodomain, probably by furin-like convertases (Wang et al. 2003). Type V collagen N-propeptide removal is partial, and reported to be mediated by BMP-1 which cleaves between the proline/arginine-rich protein domain and the variable domain of the alpha1 chain and between the small and the large collagenous domain of alpha3 chain (refs. in Colige et al. 2005). The retention of some N-propeptides occurs in a tissue specific manner and may be a mechanism to inhibit lateral fibril growth (Silver et al. 2003).
*ADAMTS2 is active against collagen types I (Lapière et al. 1971), II (Colige et al. 1995) and III (Wang et al. 2003 types I-III). ADAMTS3 has activity against type I (Le Goff 2006) and II collagen (Fernandes et al. 2001). ADAMTS14 has activity against type I collagen (Colige et al. 2002).
Locations in the PathwayBrowser
Extracellular matrix organization(Homo sapiens)