Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation-Reference-Cited by-同舟云学术

Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation

Published:2007-04-15 Issue:8 Volume:120 Page:1383-1392
ISSN:1477-9137
Container-title:Journal of Cell Science
language:en
Short-container-title:

Author:

Bax Daniel V.¹²,Mahalingam Yashithra³,Cain Stuart²,Mellody Kieran²,Freeman Lyle²,Younger Kerri²,Shuttleworth C. Adrian²,Humphries Martin J.²,Couchman John R.³,Kielty Cay M.¹²

Affiliation:

1. UK Centre for Tissue Engineering, Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK

2. Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK

3. Faculty of Medicine, Imperial College London, Exhibition Road, London, SW7 2AZ, UK

Abstract

We have defined the molecular basis of cell adhesion to fibrillin-1, the major structural component of extracellular microfibrils that are associated with elastic fibres. Using human dermal fibroblasts, and recombinant domain swap fragments containing the Arg-Gly-Asp motif, we have demonstrated a requirement for upstream domains for integrin-α5β1-mediated cell adhesion and migration. An adjacent heparin-binding site, which supports focal adhesion formation, was mapped to the fibrillin-1 TB5 motif. Site-directed mutagenesis revealed two arginine residues that are crucial for heparin binding, and confirmed their role in focal adhesion formation. These integrin and syndecan adhesion motifs juxtaposed on fibrillin-1 are evolutionarily conserved and reminiscent of similar functional elements on fibronectin, highlighting their crucial functional importance.

Publisher

The Company of Biologists

Subject

Cell Biology

Link

http://journals.biologists.com/jcs/article-pdf/120/8/1383/1371945/1383.pdf

Reference30 articles.

1. Alexopoulou, A. N., Multhaupt, H. A. and Couchman, J. R. (2007). Syndecans in wound healing, inflammation and vascular biology. Int. J. Biochem. Cell Biol.39, 505-528.

2. Baldock, C., Siegler, V., Bax, D. V., Cain, S. A., Mellody, K. T., Marson, A., Haston, J. L., Berry, R., Wang, M. C., Grossmann, J. G. et al. (2006). Nanostructure of fibrillin-1 reveals compact conformation of EGF arrays and mechanism for extensibility. Proc. Natl. Acad. Sci. USA103,11922-11927.

3. Bax, D. V., Bernard, S. E., Lomas, A., Morgan, A., Shuttleworth, C. A., Humphries, M. J. and Kielty, C. M. (2003). Cell adhesion to fibrillin-1 molecules and microfibrils is mediated by α5β1 and αvβ3 integrins. J. Biol. Chem.278,34605-34616.

4. Cain, S. A., Baldock, C., Gallagher, J., Morgan, A., Bax, D. V., Weiss, A. S., Shuttleworth, C. A. and Kielty, C. M. (2005). Fibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly. J. Biol. Chem.280,30526-30537.

5. Couchman, J. R. (2003). Syndecans: proteoglycan regulators of cell-surface microdomains? Nat. Rev. Mol. Cell Biol.4, 926-937.

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