A Role for Syndecan-1 in Coupling Fascin Spike Formation by Thrombospondin-1

Abstract

An important role of cell matrix adhesion receptors is to mediate transmembrane coupling between extracellular matrix attachment, actin reorganization, and cell spreading. Thrombospondin (TSP)-1 is a modulatory component of matrix expressed during development, immune response, or wound repair. Cell adhesion to TSP-1 involves formation of biochemically distinct matrix contacts based on stable fascin spikes. The cell surface adhesion receptors required have not been identified. We report here that antibody clustering of syndecan-1 proteoglycan specifically transduces organization of cortical actin and fascin bundles in several cell types. Transfection of COS-7 cells with syndecan-1 is sufficient to stimulate cell spreading, fascin spike assembly, and extensive protrusive lateral ruffling on TSP-1 or on syndecan-1 antibody. The underlying molecular mechanism depends on glycosaminoglycan (GAG) modification of the syndecan-1 core protein at residues S45 or S47 for cell membrane spreading and on the VC2 region of the cytoplasmic domain for spreading and fascin spike formation. Expression of the VC2 deletion mutant or GAG-negative syndecan-1 showed that syndecan-1 is necessary in spreading and fascin spike formation by C2C12 cells on TSP-1. These results establish a novel role for syndecan-1 protein in coupling a physiological matrix ligand to formation of a specific matrix contact structure.

Vitronectin's Basic Domain is a Syndecan Ligand which Functionsin transto Regulate Vitronectin Turnover

“…Several extracellular matrix proteins, including fibronectin, collagen, thrombospondin, laminin, and tenascin, interact with cell surface proteoglycans and are thought to modulate cell adhesion through this interaction (2,21,33,45,50,82). In the present study, we have shown that vitronectin also supports proteoglycan dependent cell adhesion.…”

“…Primers (2) and (3) included a silent mutation (underlined = codon; boldface = base change) which created a unique Agel restriction site designed to facilitate the identification and selection of mutant vitronectin DNA containing this deletion. PCR reactions were performed which contained either primers (1) and (3) or primers (2) and (4), together with rVn in pRc/CMV (Invitrogen, Carlsbad, CA) as a template source. The PCR reactant products were combined in a second reaction to generate a single 613 bp recombinant mutant vitronectin fragment of DNA incorporating both the deletion mutation and the histidine tag, which were verified by DNA sequencing.…”

“…Syndecan-4 binds to fibronectin and activates signaling pathways important in the assembly of focal adhesions and actin stress fibers (46,68,90). Syndecan-1 binds to thrombospondin and triggers the formation of fascin containing microspikes (2). Syndecan-2 binds to fibronectin and regulates actin organization and fibronectin matrix assembly (38,41).…”

Reception of Slit requires only the chondroitin–sulphate-modified extracellular domain of Syndecan at the target cell surface

“…The requirement for Sdc has been established for vertebrates, showing that the HSPG acts as an independent signaling receptor and has a number of functional features assigned to its cytoplasmic and extracellular domains, respectively. Its cytoplasmic domain functions in intracellular signal transduction and plays a role in the maintenance of epithelial integrity by linking the ECM to the actin cytoskeleton (9)(10)(11)(12). Furthermore, the transmembrane domain of Sdc not only serves to localize Sdc at the cell membrane but to mediate proteinprotein interactions (13).…”

Independent prognostic value of fascin immunoreactivity in stage III–IV colonic adenocarcinoma

“…Fascin, which is expressed in normal mesenchymal, endothelial, dendritic, and neuronal cells but not in normal epithelia (Kureishy et al, 2002) is important in cell -cell interactions and adhesion (Adams et al, 2001), both interacting with specific tight (Wong et al, 1999) and adherens junctions (Tao et al, 1996) and intervening in focal adhesions via b1-integrin (Jawhari et al, 2003). Moreover, the protein promotes cell locomotion (Yamashiro et al, 1998) and participates in the mechanical organisation of stress fibres (Adams, 1997).…”