title: Syndecan-1 transmembrane and extracellular domains have unique and distinct roles in cell spreading.
abstract: Raji cells expressing syndecan-1 (Raji-S1) adhere and spread when plated on heparan sulfate-binding extracellular matrix ligands or monoclonal antibody 281.2, an antibody directed against the syndecan-1 extracellular domain. Cells plated on monoclonal antibody 281.2 initially extend a broad lamellipodium, a response accompanied by membrane ruffling at the cell margin. Membrane ruffling then becomes polarized, leading to an elongated cell morphology. Previous work demonstrated that the syndecan-1 cytoplasmic domain is not required for these activities, suggesting important roles for the syndecan-1 transmembrane and/or extracellular domains in the assembly of a signaling complex necessary for spreading. Work described here demonstrates that truncation of the syndecan-1 extracellular domain does not affect the initial lamellipodial extension in the Raji-S1 cells but does inhibit the active membrane ruffling that is necessary for cell polarization. Replacement of the entire syndecan-1 transmembrane domain with leucine residues completely blocks the cell spreading. These data demonstrate that the syndecan-1 transmembrane and extracellular domains have important but distinct roles in Raji-S1 cell spreading; the extracellular domain mediates an interaction that is necessary for dynamic cytoskeletal rearrangements whereas an interaction of the transmembrane domain is required for the initial spreading response.
authors.affiliation: Department of Pathology and Laboratory Medicine and Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: McQuade
authors.forename: Alan C
authors.initials: AC
authors.lastname: Rapraeger
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000648:ultrastructure; D016764:Cell Polarity; D048429:Cell Size; D003599:Cytoskeleton; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D021962:Membrane Microdomains / Q000378:metabolism; D018715:Microscopy, Video; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D017384:Sequence Deletion; D053668:Syndecan-1; D053667:Syndecans
chemical_list: D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans