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

Daniel V Bax; Yashithra Mahalingam; Stuart Cain; Kieran Mellody; Lyle Freeman; Kerri Younger; C Adrian Shuttleworth; Martin J Humphries; John R Couchman; Cay M Kielty

doi:10.1242/jcs.003954

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

Daniel V Bax, Yashithra Mahalingam, Stuart Cain, Kieran Mellody, Lyle Freeman, Kerri Younger, C Adrian Shuttleworth, Martin J Humphries, John R Couchman, Cay M Kielty

Nutritional Immunology

61 Citations (Scopus)

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-alpha(5)beta(1)-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.

Original language	English
Journal	Journal of Cell Science
Volume	120
Issue number	Pt 8
Pages (from-to)	1383-92
Number of pages	9
ISSN	0021-9533
DOIs	https://doi.org/10.1242/jcs.003954
Publication status	Published - 2007

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Bax, D. V., Mahalingam, Y., Cain, S., Mellody, K., Freeman, L., Younger, K., Shuttleworth, C. A., Humphries, M. J., Couchman, J. R., & Kielty, C. M. (2007). Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation. Journal of Cell Science, 120(Pt 8), 1383-92. https://doi.org/10.1242/jcs.003954

Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation. / Bax, Daniel V; Mahalingam, Yashithra; Cain, Stuart et al.

In: Journal of Cell Science, Vol. 120, No. Pt 8, 2007, p. 1383-92.

Research output: Contribution to journal › Journal article › Research › peer-review

Bax, DV, Mahalingam, Y, Cain, S, Mellody, K, Freeman, L, Younger, K, Shuttleworth, CA, Humphries, MJ, Couchman, JR & Kielty, CM 2007, 'Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation.', Journal of Cell Science, vol. 120, no. Pt 8, pp. 1383-92. https://doi.org/10.1242/jcs.003954

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

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-alpha(5)beta(1)-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.",

author = "Bax, {Daniel V} and Yashithra Mahalingam and Stuart Cain and Kieran Mellody and Lyle Freeman and Kerri Younger and Shuttleworth, {C Adrian} and Humphries, {Martin J} and Couchman, {John R} and Kielty, {Cay M}",

note = "Keywords: Base Sequence; Binding Sites; Cell Adhesion; DNA Primers; Epidermal Growth Factor; Heparin; Integrin alpha5beta1; Microfilament Proteins; Mutagenesis, Site-Directed; Oligopeptides; Recombinant Proteins",

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doi = "10.1242/jcs.003954",

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AU - Bax, Daniel V

AU - Mahalingam, Yashithra

AU - Cain, Stuart

AU - Mellody, Kieran

AU - Freeman, Lyle

AU - Younger, Kerri

AU - Shuttleworth, C Adrian

AU - Humphries, Martin J

AU - Couchman, John R

AU - Kielty, Cay M

N1 - Keywords: Base Sequence; Binding Sites; Cell Adhesion; DNA Primers; Epidermal Growth Factor; Heparin; Integrin alpha5beta1; Microfilament Proteins; Mutagenesis, Site-Directed; Oligopeptides; Recombinant Proteins

PY - 2007

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N2 - 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-alpha(5)beta(1)-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.

AB - 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-alpha(5)beta(1)-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.

U2 - 10.1242/jcs.003954

DO - 10.1242/jcs.003954

M3 - Journal article

C2 - 17374638

SN - 0021-9533

VL - 120

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EP - 1392

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - Pt 8

ER -

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

Abstract

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