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The Streptococcal Collagen-binding Protein CNE Specifically Interferes with alpha(V)beta(3)-mediated Cellular Interactions with Triple Helical Collagen

van Wieringen, Tijs; Kalamajski, Sebastian; Liden, Asa; Bihan, Dominique; Guss, Bengt; Heinegård, Dick LU ; Farndale, Richard W. and Rubin, Kristofer (2010) In Journal of Biological Chemistry 285(46). p.35803-35813
Abstract
Collagen fibers expose distinct domains allowing for specific interactions with other extracellular matrix proteins and cells. To investigate putative collagen domains that govern integrin alpha(V)beta(3)-mediated cellular interactions with native collagen fibers we took advantage of the streptococcal protein CNE that bound native fibrillar collagens. CNE specifically inhibited alpha(V)beta(3)-dependent cell-mediated collagen gel contraction, PDGF BB-induced and alpha(V)beta(3)-mediated adhesion of cells, and binding of fibronectin to native collagen. Using a Toolkit composed of overlapping, 27-residue triple helical segments of collagen type II, two CNE-binding sites present in peptides II-1 and II-44 were identified. These peptides lack... (More)
Collagen fibers expose distinct domains allowing for specific interactions with other extracellular matrix proteins and cells. To investigate putative collagen domains that govern integrin alpha(V)beta(3)-mediated cellular interactions with native collagen fibers we took advantage of the streptococcal protein CNE that bound native fibrillar collagens. CNE specifically inhibited alpha(V)beta(3)-dependent cell-mediated collagen gel contraction, PDGF BB-induced and alpha(V)beta(3)-mediated adhesion of cells, and binding of fibronectin to native collagen. Using a Toolkit composed of overlapping, 27-residue triple helical segments of collagen type II, two CNE-binding sites present in peptides II-1 and II-44 were identified. These peptides lack the major binding site for collagen-binding beta(1) integrins, defined by the peptide GFOGER. Peptide II-44 corresponds to a region of collagen known to bind collagenases, discoidin domain receptor 2, SPARC (osteonectin), and fibronectin. In addition to binding fibronectin, peptide II-44 but not II-1 inhibited alpha(V)beta(3)-mediated collagen gel contraction and, when immobilized on plastic, supported adhesion of cells. Reduction of fibronectin expression by siRNA reduced PDGF BB-induced alpha(V)beta(3)-mediated contraction. Reconstitution of collagen types I and II gels in the presence of CNE reduced collagen fibril diameters and fibril melting temperatures. Our data indicate that contraction proceeded through an indirect mechanism involving binding of cell-produced fibronectin to the collagen fibers. Furthermore, our data show that cell-mediated collagen gel contraction does not directly depend on the process of fibril formation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
285
issue
46
pages
35803 - 35813
publisher
ASBMB
external identifiers
  • wos:000283845300058
  • scopus:78149235448
ISSN
1083-351X
DOI
10.1074/jbc.M110.146001
language
English
LU publication?
yes
id
248f8d72-3903-4c85-8607-47e0b957b866 (old id 1752438)
date added to LUP
2011-01-04 07:34:28
date last changed
2018-05-29 10:08:18
@article{248f8d72-3903-4c85-8607-47e0b957b866,
  abstract     = {Collagen fibers expose distinct domains allowing for specific interactions with other extracellular matrix proteins and cells. To investigate putative collagen domains that govern integrin alpha(V)beta(3)-mediated cellular interactions with native collagen fibers we took advantage of the streptococcal protein CNE that bound native fibrillar collagens. CNE specifically inhibited alpha(V)beta(3)-dependent cell-mediated collagen gel contraction, PDGF BB-induced and alpha(V)beta(3)-mediated adhesion of cells, and binding of fibronectin to native collagen. Using a Toolkit composed of overlapping, 27-residue triple helical segments of collagen type II, two CNE-binding sites present in peptides II-1 and II-44 were identified. These peptides lack the major binding site for collagen-binding beta(1) integrins, defined by the peptide GFOGER. Peptide II-44 corresponds to a region of collagen known to bind collagenases, discoidin domain receptor 2, SPARC (osteonectin), and fibronectin. In addition to binding fibronectin, peptide II-44 but not II-1 inhibited alpha(V)beta(3)-mediated collagen gel contraction and, when immobilized on plastic, supported adhesion of cells. Reduction of fibronectin expression by siRNA reduced PDGF BB-induced alpha(V)beta(3)-mediated contraction. Reconstitution of collagen types I and II gels in the presence of CNE reduced collagen fibril diameters and fibril melting temperatures. Our data indicate that contraction proceeded through an indirect mechanism involving binding of cell-produced fibronectin to the collagen fibers. Furthermore, our data show that cell-mediated collagen gel contraction does not directly depend on the process of fibril formation.},
  author       = {van Wieringen, Tijs and Kalamajski, Sebastian and Liden, Asa and Bihan, Dominique and Guss, Bengt and Heinegård, Dick and Farndale, Richard W. and Rubin, Kristofer},
  issn         = {1083-351X},
  language     = {eng},
  number       = {46},
  pages        = {35803--35813},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {The Streptococcal Collagen-binding Protein CNE Specifically Interferes with alpha(V)beta(3)-mediated Cellular Interactions with Triple Helical Collagen},
  url          = {http://dx.doi.org/10.1074/jbc.M110.146001},
  volume       = {285},
  year         = {2010},
}