Syndecan-1 regulates αvβ5 integrin activity in B82L fibroblasts

Kyle J. McQuade, Deanna Lee M. Beauvais, Brandon J. Burbach, Alan C. Rapraeger

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

B82L mouse fibroblasts respond to fibronectin or vitronectin via a syndecan-1-mediated activation of the αvβ5 integrin. Cells attached to syndecan-1-specific antibody display only filopodial extension. However, the syndecan-anchored cells extend lamellipodia when the antibody-substratum is supplemented with serum, or low concentrations of adsorbed vitronectin or fibronectin, that are not sufficient to activate the integrin when plated alone. Integrin activation is blocked by treatment with (Arg-Gly-Asp)-containing peptides and function-blocking antibodies that target αv integrins, as well as by siRNA-mediated silencing of β'5 integrin expression. In addition, αvβ5-mediated cell attachment and spreading on high concentrations of vitronectin is blocked by competition with recombinant syndecan-1 ectodomain core protein and by downregulation of mouse syndecan-1 expression by mouse-specific siRNA. Taking advantage of the species-specificity of the siRNA, rescue experiments in which human syndecan-1 constructs are expressed trace the activation site to the syndecan-I ectodomain. Moreover, both full-length mouse and human syndecan-1 co-immunoprecipitate with the β5 integrin subunit, but fail to do so if the syndecan is displaced by competition with soluble, recombinant syndecan-1 ectodomain. These results suggest that the ectodomain of the syndecan-1 core protein contains an active site that assembles into a complex with the αvβ5 integrin and regulates αvβ5 integrin activity.

Original languageEnglish (US)
Pages (from-to)2445-2456
Number of pages12
JournalJournal of cell science
Volume119
Issue number12
DOIs
StatePublished - Jun 15 2006

Keywords

  • Cell adhesion
  • Extracellular matrix
  • Proteoglycan
  • Syndecan-1
  • Vitronectin
  • αβ integrin

Fingerprint Dive into the research topics of 'Syndecan-1 regulates α<sub>v</sub>β<sub>5</sub> integrin activity in B82L fibroblasts'. Together they form a unique fingerprint.

Cite this