syndecan3

Syndecan-3 (SDC3), also known as N-syndecan, is a member of the syndecan family of transmembrane heparan sulfate proteoglycans. Like other syndecans, SDC3 has a single-pass transmembrane core protein with covalently attached heparan sulfate chains on the extracellular domain that bind a wide range of ligands, including growth factors, morphogens, cytokines, and extracellular matrix components. Its cytoplasmic tail contains conserved regions that interact with intracellular adapters and the actin cytoskeleton, helping to couple extracellular signals to intracellular pathways.

Expression of SDC3 is highest in the nervous system, particularly in certain neurons in the brain such as the hippocampus and cortex, though it is also found in other tissues at lower levels. Functionally, SDC3 participates in neural development and synaptic organization by regulating neurite outgrowth, axon guidance, and synapse formation. It modulates signaling by presenting or concentrating ligands for receptors such as fibroblast growth factor receptors and Wnt pathway components at the cell surface, and it can influence interactions with extracellular matrix proteins, influencing adhesion and migration.

Regulation of SDC3 includes proteolytic shedding of its ectodomain, producing a soluble fragment that may exert extracellular effects. The cytoplasmic tail can recruit scaffolding and signaling proteins, linking the proteoglycan to cytoskeletal dynamics and intracellular signaling cascades.

In humans, the SDC3 gene encodes the SDC3 core protein. Research has investigated roles for SDC3 in neural development and, in animal models, possible involvement in energy balance and feeding behavior, though its precise physiological functions in humans require further clarification.