syndecan4

Syndecan-4, abbreviated SDC4, is a transmembrane heparan sulfate proteoglycan that belongs to the syndecan family. In humans, the SDC4 gene encodes the core protein, which is broadly expressed and participates in cell–matrix adhesion and signal transduction.

The protein has an extracellular domain bearing covalently attached heparan sulfate chains, a single-pass transmembrane segment, and a short cytoplasmic tail of about 30 amino acids that contains a conserved EFYA motif. This cytoplasmic tail interacts with PDZ-domain proteins and cytoskeletal regulators, linking extracellular cues to intracellular signaling and organization.

Functions of syndecan-4 include regulation of focal adhesion formation and actin cytoskeleton organization, influencing cell spreading, adhesion, and migration. It modulates signaling pathways initiated by growth factor receptors and integrins and participates in processes such as wound healing, angiogenesis, and inflammatory responses. The interactions of its heparan sulfate chains with ligands help concentrate and present signaling molecules at the cell surface.

Ligand interactions involve various extracellular ligands that bind heparan sulfate chains, including fibronectin and growth factors like FGF and VEGF, as well as chemokines. Intracellularly, syndecan-4 communicates with protein kinase C alpha (PKCα) and cytoskeletal adaptors, enabling mechanotransduction and coordination of adhesion and movement.

Clinical and research relevance: Syndecan-4 is studied for its roles in cancer progression, fibrosis, and tissue repair, where altered expression or function can influence cell behavior and remodeling. Animal and cellular studies continue to clarify its contributions to adhesion, signaling, and vascular remodeling across tissues.