5Centro de Biologia Ambiental/Departamento de Biologia Animal, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal
Summary
Introduction
This discrepancy was solved when bigger molecular species had been purified from chick fibroblasts (Koch et al., 1992) and a human cell line (Lunstrum et al., 1992), and proven to be collagen XII variants by peptide sequencing. Later, van der Relaxation and colleagues characterised the intact protein as homotrimer of 220-kDa subunits, with disulfide-bonded 190-kDa noncollagenous domains linked to a brief C-terminal collagen helix (Dublet et al., 1989). Single collagen XII molecules from tendon appeared cross-shaped with three 60 nm lengthy arms and a thinner tail 75 nm in size (Dublet et al., 1989).
Construction: “Large” (XIIA) versus “small” (XIIB) collagen XII variants
Lastly, it’s noteworthy that heterotrimeric collagen XII molecules assembled from XIIA and XIIB variants could be remoted (Koch et al., 1995; Fig. 1C). The next area, homologous to the NC4 area of collagen IX, hyperlinks collagen XII subunits by disulfide bridges. In direction of their C-terminus, three subunits intertwine in a brief collagen helix that’s interrupted by a small NC2 and ends in a NC1 area.
Expression: Regulation by development components and mechanical stress
Apparently, a distinct enhancer area seems to be required for activation of the murine Col12a1 gene by cyclic pressure in osteoblasts, specifically an AP1 website binding c-Jun and JunD after pressure (Arai et al., 2008). Within the chick COL12A1 promoter, an enhancer area attentive to static tensile pressure was recognized within the first exon (Chiquet et al., 1998). In vivo, collagen XII is induced upon power muscle loading (Fluck et al., 2000), and in periodontal ligament throughout orthodontic tooth motion (Karimbux and Nishimura, 1995).
Organic perform: Group of collagen I fibrils and function in osteogenesis
Second, cross-striated fibrils embellished with collagen XII might be reconstituted in vitro by co-assembly of collagen I monomers with purified collagen XII (Koch et al., 1995). With its collagenous area, collagen XII additionally binds decorin, fibromodulin (Font et al., 1996) and cartilage oligomeric matrix protein (COMP) (Agarwal et al., 2012), all of that are discovered on the floor of collagen fibrils. Accordingly, collagen XII was proven to advertise the contraction of collagen I gels by fibroblasts not by activating cells instantly, however by altering the mobility of fibrils throughout the gel (Nishiyama et al., 1994).
Scientific relevance: COL12A1 mutations inflicting EDS/myopathy overlap syndrome
Furthermore, they set up an informative hyperlink between the intriguing construction and molecular interactions of this FACIT and its perform in sustaining extracellular matrix integrity in load-bearing connective tissues of the locomotory system. In abstract, these new findings show that mutations in collagen XII are causative for human connective tissue pathologies.