SYNTENIN, A PDZ PROTEIN THAT BINDS SYNDECAN CYTOPLASMIC DOMAINS

The syndecans are transmembrane proteoglycans that place structurally heterogeneous heparan sulfate chains at the cell surface and a highly conserved polypeptide in the cytoplasm. Their versatile heparan sulfat e moieties support various processes of molecular recognition, signali ng, and trafficking. Here we report the identification of a protein th at binds to the cytoplasmic domains of the syndecans in yeast two-hybr id screens, surface plasmon resonance experiments, and ligand-overlay assays. This protein, syntenin, contains a tandem repeat of PDZ domain s that reacts with the FYA C-terminal amino acid sequence of the synde cans. Recombinant enhanced green fluorescent protein (eGFP)-syntenin f usion proteins decorate the plasmamembrane and intracellular vesicles, where they colocalize and cosegregate with syndecans. Cells that over express eGFP-syntenin show numerous cell surface extensions, suggestin g effects of syntenin on cytoskeleton-membrane organization. We propos e that syntenin may function as an adaptor that couples syndecans to c ytoskeletal proteins or cytosolic downstream signal-effectors.