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Integrin mediated cell adhesion to the syndecan‐4 ectodomain requires N‐glycosylation and phosphatases.
Author(s) -
Whiteford James,
Couchman John
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.274
Subject(s) - ectodomain , microbiology and biotechnology , integrin , syndecan 1 , protein tyrosine phosphatase , cell adhesion , cell adhesion molecule , focal adhesion , adhesion , chemistry , biology , signal transduction , biochemistry , cell , receptor , organic chemistry
Well documented is the contribution of syndecan‐4 that interacts through its heparan sulphate chains to promote focal adhesion formation in fibroblasts in response to fibronectin domains. Essential to this process is engagement of alpha5 beta1 integrin and syndecan‐4 signalling. We have shown that an alternate pathway to focal adhesion formation is mediated by the extracellular domains of syndecan ‐4 that is heparan sulphate and syndecan‐4 signalling independent. The syndecan‐4 ectodomain promotes integrin mediated attachment, spreading and focal adhesion formation in mesenchymal but not epithelial cells. The interaction between integrins and syndecan ectodomains is indirect and for this reason we have proposed the existence of an intermediate(s) protein which mediates the interaction between syndecan ectodomains and integrins. Here we show that cell adhesion to syndecan ectodomains is dependant on N‐glycosylation and that phosphatase activity is necessary. We screened a library of 205 siRNAs to 205 human phosphatase genes to determine which phosphatases were important for adhesion to the syndecan‐4 ectodomain. Several potential targets were identified most notably three receptor protein tyrosine phosphatases. We present further validation of these targets and try to elucidate further the identity of the proteins which mediate integrin dependant adhesion to syndecan ectodomains.