Syndesmos, a protein that interacts with the cytoplasmic domain of syndecan-4, mediates cell spreading and actin cytoskeletal organization

Syndecan-4 is a cell surface heparan sulfate proteoglycan which, in coopera tion with integrins, transduces signals for the assembly of focal adhesions and actin stress fibers in cells plated on fibronectin. The regulation of these cellular events is proposed to occur, in part, through the interactio n of the cytoplasmic domains of these transmembrane receptors with intracel lular proteins. To identify potential intracellular proteins that interact with the cytoplasmic domain of syndecan-4, we carried out a yeast two-hybri d screen in which the cytoplasmic domain of syndecan-4 was used as bait. As a result of this screen, we have identified a novel cellular protein that interacts with the cytoplasmic domain of syndecan-4 but not with those of t he other three syndecan family members. The interaction involves both the m embrane proximal and variable central regions of the cytoplasmic domain. We have named this cDNA and encoded protein syndesmos, Syndesmos is ubiquitou sly expressed and can be myristylated. Consistent with its myristylation an d syndecan-4 association, syndesmos colocalizes with syndecan-4 in the vent ral plasma membranes of cells plated on fibronectin. When overexpressed in NIH 3T3 cells, syndesmos enhances cell spreading, actin stress fiber and fo cal contact formation in a serum-independent manner.