The Streptococcal Collagen-binding Protein CNE Specifically Interferes with alpha(V)beta(3)-mediated Cellular Interactions with Triple Helical Collagen
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1752438
- author
- van Wieringen, Tijs ; Kalamajski, Sebastian ; Liden, Asa ; Bihan, Dominique ; Guss, Bengt ; Heinegård, Dick LU ; Farndale, Richard W. and Rubin, Kristofer
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 285
- issue
- 46
- pages
- 35803 - 35813
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000283845300058
- scopus:78149235448
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M110.146001
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Connective Tissue Biology (013230151)
- id
- 248f8d72-3903-4c85-8607-47e0b957b866 (old id 1752438)
- date added to LUP
- 2016-04-01 10:48:23
- date last changed
- 2022-01-26 02:38:16
@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 = {{American Society for Biochemistry and Molecular Biology}},
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}},
doi = {{10.1074/jbc.M110.146001}},
volume = {{285}},
year = {{2010}},
}