Control of morphology, cytoskeleton and migration by syndecan-4.
Syndecan-4 is a widely expressed transmembrane heparan sulfate proteoglycan which localizes to focal adhesions. Previous studies showed that the syndecan-4 cytoplasmic domain can associate with and potentiate the activity of protein kinase C, which is required for focal adhesion formation. To examine further the role of syndecan-4 in cell adhesion, we expressed syndecan-4 cDNA constructs in CHO-K1 cells. Syndecan-2 transfection was used to confirm effects seen were specific for syndecan-4. Cells overexpressing full length syndecan-4 core protein exhibited a more flattened, fibroblastic morphology, with increased focal adhesion formation and decreased cell motility. Expression of a syndecan-4 core protein with either a partial or complete deletion of the cytoplasmic domain or of an antisense construct led to markedly decreased spreading and focal adhesion formation, a more epithelioid morphology, and decreased motility. Overexpression of syndecan-2 changed the adhesive phenotype, but did not markedly alter focal adhesion and microfilament bundle formation. The data suggest that syndecan-4 is a regulator of focal adhesion and stress fiber formation, and influences both morphology and migration.
Longley
R L
RL
Department of Cell Biology and Cell Adhesion and Matrix Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA. jrcouchman@cellbio.bhs.uab.edu
Woods
A
A
Fleetwood
A
A
Cowling
G J
GJ
Gallagher
J T
JT
Couchman
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division; D048429:Cell Size; D002633:Chemotaxis; D006224:Cricetinae; D003599:Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005434:Flow Cytometry; D008099:Liver / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011493:Protein Kinase C / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D053669:Syndecan-2; D053671:Syndecan-4; D014162:Transfection
D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011994:Recombinant Proteins; C508247:Sdc2 protein, rat; C508307:Sdc4 protein, rat; D053671:Syndecan-4; D053669:Syndecan-2; D011493:Protein Kinase C