1,721,193 research outputs found
The carboxyl terminus of the chicken alpha3 chain of collagen VI is a unique mosaic structure with glycoprotein Ib-like, fibronectin type III, and Kunitz modules.
No full textThe primary amino acid sequence of the carboxyl-terminal portion of the alpha 3 chain of chick type VI collagen as deduced from the nucleotide sequence is reported. This carboxyl-terminal segment is not present in the alpha 1 and alpha 2 chains of chick type VI collagen and is specific for a mosaic region with extensive similarities to several other proteins. This unique segment, beginning with a stretch (73 residues) very rich in serine and threonine, is preceded by sequences analogous to the platelet glycoprotein Ib. This region is followed by one segment that closely resembles the type III domains of fibronectin. At the end of the sequence, there is a 58-residue motif very similar to sequences characteristic of the Kunitz-type proteinase inhibitors. The present findings and our recent observation that the alpha 3(VI) chain contains 11 repeats similar to type A repeats of von Willebrand factor raise interesting questions about the peculiar mosaic structure and the multiple functions that this unique collagen might play in growth and remodeling of connective tissues
Biosynthesis of chick type VI collagen. II: Processing and secretion in fibroblasts and smooth muscle cells.
No full textThe biosynthesis of type VI collagen was studied in "matrix-free" chick embryo smooth muscle cells and fibroblasts. Omission of ascorbate from the culture affected to a great extent the secretion in fibroblasts but had a very minor effect on smooth muscle cells. Quantitative analysis of the secretion process in continuous time course and in pulse-chase experiments confirmed that fibroblasts and smooth muscle cells secreted type VI collagen with the same chain composition but with different kinetics: after 4 h of chase more than 60% of the labeled type VI collagen was present in the culture medium of fibroblasts, whereas at the same time interval less than 25% was secreted by smooth muscle cells. The different kinetics depends on intrinsic properties of the cells, since it was detected also in adherent cells. However, even in fibroblasts, secretion of type VI collagen was much slower than secretion of fibronectin, of which more than 50% was already in the cell medium after 1 h of chase. Treatment of the cells with inhibitors of hydroxylation and glycosylation caused a shift in mobility that revealed a size heterogeneity in the Mr = 260,000 subunit. No evidence of processing was observed in chick cells for any of the subunits that were synthesized and secreted uncleaved. In addition, after several days of chase the Mr of the subunits of type VI collagen isolated from the matrix remained unchanged, thus excluding that in the chick even a partial or incomplete processing takes place
The superfamily of proteins with von Willebrand Factor type A-like domains: one theme common to components of extracellular matrix, hemostasis, cellular adhesion, and defense mechanisms.
No full textMitochondrial dysfunction and defective autophagy in the pathogenesis of collagen VI muscular dystrophies.
No full textUllrich Congenital Muscular Dystrophy (UCMD), Bethlem Myopathy (BM) and Congenital Myosclerosis are diseases due to mutations in the genes encoding the extracellular matrix protein collagen VI. A dystrophic mouse model where collagen VI synthesis was prevented by targeted inactivation of the Col6a1 gene allowed the investigation of pathogenesis, which revealed the existence of a Ca2+-mediated dysfunction of mitochondria and sarcoplasmic reticulum, and of defective autophagy. Key events are dysregulation of the mitochondrial permeability transition pore, an inner membrane high-conductance channel that for prolonged open times causes mitochondrial dysfunction; and inadequate removal of defective mitochondria, which amplifies the damage. Consistently, the Col6a1-/- myopathic mice could be cured with through inhibition of cyclophilin D, a matrix protein that sensitizes the pore to opening, and through stimulation of autophagy. Similar defects contribute to disease pathogenesis in patients irrespective of the genetic lesion causing the collagen VI defect. These studies indicate that PTP opening and defective autophagy represent key elements for skeletal muscle fiber death, and provide a rationale for the use of cyclosporin A and its non immunosuppressive derivatives in patients affected by collagen VI myopathies, a strategy that holds great promise for treatment
Type A modules: interacting domains found in several non-fibrillar collagens and in other extracellular matrix proteins.
No full textA 200-amino acid long motif first recognized in von Willebrand Factor (type A module) has been found in components of the extracellular matrix, hemostasis, cellular adhesion, and immune defense mechanisms. At present the extracellular matrix is the predominant site of expression of type A modules since at least four non-fibrillar collagens and two non-collagenous proteins contain a variable number of modules ranging from one to twelve. The modules conform to a consensus motif made of short conserved subregions separated by stretches of variable length. The proteins that incorporate type A modules participate in numerous biological events such as cell adhesion, migration, homing, pattern formation, and signal transduction after interaction with a large array of ligands
Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury.
No full textSecretion and matrix assembly of recombinant type VI collagen.
No full textA monomer of type VI collagen is composed of three different chains of 140 (alpha 1), 130 (alpha 2), and 250-350 kDa (alpha 3). Monomers assemble into dimers (6 chains) and tetramers (12 chains) that are stabilized by disulfide bonds and, once associated one to another, give rise to a microfilamentous network in close apposition with cell surfaces and banded collagen fibers. We have derived murine NIH/3T3 cell lines that were transfected with the cDNAs for the three chains and that constitutively expressed chicken type VI collagen. Cotransfection was efficient because, in three out of six isolated cell lines, all chicken chains were expressed. Southern blotting demonstrated that several copies of each cDNA were integrated approximately in equal number. Expression of the three polypeptide chains was consistent with the levels of the respective mRNAs. The three chicken chains assembled by disulfide bonding to form correctly folded triple helical aggregated composites with sizes corresponding to type VI collagen monomers, dimers, and tetramers. These functional recombinant assemblies were secreted and became incorporated into the extracellular matrix, where they formed an extensive fibrillar network
Isolation of cDNA clones corresponding to the Mr=150,000 subunit of chick type VI collagen.
No full textType VI collagen is a disulfide-bonded protein with an unusual structure in that the molecule contains three short triple-helical domains and very extended non-collagenous regions. The molecule is a heterotrimer composed in the chick of two polypeptides of similar apparent size in SDS-PAGE (Mr = 140- and 150,000) but different structure, and a third component that is much larger (Mr = 260,000) than the other two chains. We report here on the isolation of several overlapping cDNA clones from a chicken aorta mRNA expression library in the plasmid vector pEX1. Antibodies affinity purified onto the fusion proteins recognized the chick type VI collagen Mr = 150,000 subunit. Northern blots using the cDNA inserts from the above clones revealed a single RNA species of about 4,600 nucleotides sufficient to code for a protein with the size of the Mr = 150,000 subunit
- …
