Syndesmos, a Syndecan-4 Cytoplasmic Domain Interactor, Binds to the Focal Adhesion Adaptor Proteins Paxillin and Hic-5

Abstract

Syndecan-4 and integrins are the primary transmembrane receptors of focal adhesions in cells adherent to extracellular matrix molecules. Syndesmos is a cytoplasmic protein that interacts specifically with the cytoplasmic domain of syndecan-4, and it co-localizes with syndecan-4 in focal contacts. In the present study we sought possible interactors with syndesmos. We find that syndesmos interacts with the focal adhesion adaptor protein paxillin. The binding of syndesmos to paxillin is direct, and these interactions are triggered by the activation of protein kinase C. Syndesmos also binds the paxillin homolog, Hic-5. The connection of syndecan-4 with paxillin through syndesmos parallels the connection between paxillin and integrins and may thus reflect the cooperative signaling of these two receptors in the assembly of focal adhesions and actin stress fibers.

Defining the role of syndecan-4 in mechanotransduction using surface-modification approaches

“…They have been linked with local domain protein distribution and binding to cytoplasmic proteins and are involved in intracellular phosphorylation (20). Furthermore, syndecan binding has been shown to play a role in a wide variety of functional areas including the activation of the Rho and Rac pathways (16,21). This finding indicates the possibility of a progressive sequence that could lead to the activation of ERK phosphorylations, because both Rho and Rac are part of the integrin mechanotransduction pathway as well.…”

“…Furthermore, syndecan-4 molecules are also known to be a component of the FAC (17), which is very important for communication across the cell membrane during mechanotransduction. Syndecan-4 molecules have been shown to indirectly attach to primary protein components of the FAC, including paxillin, that is linked to the actin cytoskeleton (16). In addition, studies have already indicated that heparin sulfate-linked proteins could have a role in mechanical signaling (15) and have been implicated in numerous processes from cell signaling to adhesion (18).…”

Tenascin-C blocks cell-cycle progression of anchorage-dependent fibroblasts on fibronectin through inhibition of syndecan-4

“…Wade et al (2002) showed that paxillin is required for the attachment-dependent phosphorylation of FAK in early cell spreading of ES cells while Denhez et al (2002) demonstrated binding of paxillin to syndecan-4 through syndesmos. Thus paxillin might be crucial for integrin-and syndecan-4-mediated FAK activation, sequestering them into proximity within focal adhesions.…”

Combined Lysophosphatidic Acid/Platelet-Derived Growth Factor Signaling Triggers Glioma Cell Migration in a Tenascin-C Microenvironment

“…Integrins are linked to paxillin in complexes containing talin, FAK, among other molecules (13). Paxillin binds syndesmos, which itself interacts with the cytoplasmic tail of syndecan-4 (14), thus forming a molecular bridge between integrin a 5 h 1 and syndecan-4. Paxillin and FAK are critically involved in cell spreading and integrate signals from different transmembrane receptors, including integrins and the platelet-derived growth factor receptor (PDGFR; refs.…”