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The laboratory of Dr. Myers' is working on the structure and expression of two very rare collagen proteins (types XV and XIX) discovered from the sequence of cDNA clones. By immunohistochemistry, both have been shown to be closely associated with basement membranes in a wide variety of human tissues. There is considerable evidence that these collagens possess specialized signaling and structural roles not previously associated with the collagen family. Type XV collagen functions as a high molecular weight proteoglycan with chondroitin and heparan sulfate chains attached to the amino-terminal domain. A carboxy-terminal fragment cleaved from the intact chain may be an inhibitor of angiogenesis. Type XIX collagen has a particularly unique distribution in cells undergoing skeletal muscle differentiation. In vitro and in vivo models of this process together with the up-regulation of type XIX and myogenic transcription factors is currently being studied. We have recently purified type XIX from human umbilical cords and demonstrated by electron microscopy and biochemical analysis that the molecule is highly polymorphic and can adopt a countless number of configurations. Supramolecular aggregates were also identified and shown to originate from interaction via the globular amino-terminal domain, which possesses a high affinity heparin-binding site. Selected Publications: Amenta, P.S., Scivoletti, N.A., Newman, M.D., Sciancalepore, J.P., Li, D., and Myers, J.C. (2005) Proteoglycan-collagen XV in human tissues is seen linking banded collagen fibers subjacent to the basement membrane. J. Histochem. Cytochem. 53:165-176 Myers, J.C., Li, D., Amenta, P.S., Clark, C.C., Nagaswami, C., and Weisel, J.W. (2003) Type XIX collagen purified from human umbilical cord is characterized by multiple sharp kinks delineating collagenous subdomains and by intermolecular aggregates via globular, disulfide-linked, and heparin-binding amino termini. J. Biol. Chem. 278:32047-32057 Li, D., Clark, C.C. and Myers, J. C. (2000) Basement membrane zone type XV collagen is a disulfide-bonded chondroitin sulfate proteoglycan in human tissues and cultured cells. J. Biol. Chem. 275:22339-22347 Myers, J.C., Li, D., Rubinstein, N.A., and Clark, C.C. (1999) Up regulation of type XIX collagen in rhabdomyosarcoma cells accompanies myogenic differentiation. Exp. Cell Res. 153:587-598. |
