Syntenin

Syntenin, also known as syntenin-1, is a cytosolic adaptor protein encoded by the SDCBP gene in humans. It is characterized by two PDZ domains (PDZ1 and PDZ2) in its N-terminal region and a C-terminal tail. Through the PDZ domains, syntenin binds to the cytoplasmic tails of syndecans (SDC1–SDC4) and to a variety of other transmembrane or intracellular proteins that end with PDZ-binding motifs, enabling it to organize multi-protein complexes at the cell surface and in endosomal compartments.

Syntenin participates in cargo trafficking, including receptor endocytosis, recycling, and sorting. A major pathway involves exosome biogenesis, in which syntenin links syndecan-bound cargos to the ESCRT machinery via the protein ALIX, promoting incorporation of cargo into intraluminal vesicles and exosome release.

In cellular signaling, syntenin serves as a scaffold that coordinates interactions among receptors, cytoskeletal regulators, and signaling enzymes, influencing processes such as cell adhesion, migration, and synaptic organization in neurons. Its function is context-dependent and tissue-specific.

Dysregulation of syntenin expression or interactions has been associated with cancer progression and metastasis in several tumor types, reflecting its role in modulating cell communication and motility. Syntenin is conserved across vertebrates and acts as a hub for protein-protein interactions that connect membrane proteins to cytosolic signaling networks.