TY - JOUR
T1 - Syndecans promote integrin-mediated adhesion of mesenchymal cells in two distinct pathways.
AU - Whiteford, James
AU - Behrends, Volker
AU - Kirby, Hishani
AU - Kusche-Gullberg, Marion
AU - Muramatsu, Takashi
AU - Couchman, John R
N1 - Keywords: Animals; COS Cells; Cell Adhesion; Cell Line; Cercopithecus aethiops; Endothelial Cells; Fibroblasts; Focal Adhesions; Heparitin Sulfate; Humans; Integrins; Jurkat Cells; Mesoderm; Mice; Protein Structure, Tertiary; Rats; Syndecan-2; Syndecan-4; rho-Associated Kinases
PY - 2007
Y1 - 2007
N2 - Syndecans are transmembrane proteoglycans that support integrin-mediated adhesion. Well documented is the contribution of syndecan-4 that interacts through its heparan sulphate chains to promote focal adhesion formation in response to fibronectin domains. This process has requirements for integrin and signaling through the cytoplasmic domain of syndecan-4. Here an alternate pathway mediated by the extracellular domains of syndecans-2 and -4 is characterized that is independent of both heparan sulphate and syndecan signaling. This pathway is restricted to mesenchymal cells and was not seen in any epithelial cell line tested, apart from vascular endothelia. The syndecan ectodomains coated as substrates promoted integrin-dependent attachment, spreading and focal adhesion formation. Syndecan-4 null cells were competent, as were fibroblasts compromised in heparan sulphate synthesis that were unable to form focal adhesions in response to fibronectin. Consistent with actin cytoskeleton organization, the process required Rho-GTP and Rho kinase. While syndecan-2 and -4 ectodomains could both promote integrin-mediated adhesion, their pathways were distinct, as shown by competition assays. Evidence for an indirect interaction of beta1 integrin with both syndecan ectodomains was obtained, all of which suggests a distinct mechanism of integrin-mediated adhesion.
AB - Syndecans are transmembrane proteoglycans that support integrin-mediated adhesion. Well documented is the contribution of syndecan-4 that interacts through its heparan sulphate chains to promote focal adhesion formation in response to fibronectin domains. This process has requirements for integrin and signaling through the cytoplasmic domain of syndecan-4. Here an alternate pathway mediated by the extracellular domains of syndecans-2 and -4 is characterized that is independent of both heparan sulphate and syndecan signaling. This pathway is restricted to mesenchymal cells and was not seen in any epithelial cell line tested, apart from vascular endothelia. The syndecan ectodomains coated as substrates promoted integrin-dependent attachment, spreading and focal adhesion formation. Syndecan-4 null cells were competent, as were fibroblasts compromised in heparan sulphate synthesis that were unable to form focal adhesions in response to fibronectin. Consistent with actin cytoskeleton organization, the process required Rho-GTP and Rho kinase. While syndecan-2 and -4 ectodomains could both promote integrin-mediated adhesion, their pathways were distinct, as shown by competition assays. Evidence for an indirect interaction of beta1 integrin with both syndecan ectodomains was obtained, all of which suggests a distinct mechanism of integrin-mediated adhesion.
U2 - 10.1016/j.yexcr.2007.08.002
DO - 10.1016/j.yexcr.2007.08.002
M3 - Journal article
C2 - 17870067
SN - 0014-4827
VL - 313
SP - 3902
EP - 3913
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 18
ER -