Syntenin, a PDZ Protein that Binds Syndecan Cytoplasmic Domains

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 25; pp. 13683 - 13688
• Main Authors: Grootjans, Johan J., Zimmermann, Pascale, Reekmans, Gunter, Smets, An, Degeest, Gisele, Durr, Joachim, David, Guido
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 09.12.1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Amino Acid Sequence; Amino acids; Animals; Binding Sites - genetics; Biological Sciences; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Membrane - metabolism; Cells; Cellular biology; CHO Cells; Cricetinae; Cytoskeleton - metabolism; Humans; In Vitro Techniques; Intracellular Signaling Peptides and Proteins; Ligands; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane Proteins; Mice; Microscopy, Fluorescence; Molecular Sequence Data; Plasmids; Protein Binding; Proteins; Proteoglycans - chemistry; Proteoglycans - genetics; Proteoglycans - metabolism; Receptors; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Saccharomyces cerevisiae - genetics; Sequence Homology, Amino Acid; Sulfates; Syndecan-2; Syntenins; Yeast; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.25.13683

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 sulfate moieties support various processes of molecular recognition, signaling, and trafficking. Here we report the identification of a protein that binds to the cytoplasmic domains of the syndecans in yeast two-hybrid screens, surface plasmon resonance experiments, and ligand-overlay assays. This protein, syntenin, contains a tandem repeat of PDZ domains that reacts with the FYA C-terminal amino acid sequence of the syndecans. Recombinant enhanced green fluorescent protein (eGFP)--syntenin fusion proteins decorate the plasmamembrane and intracellular vesicles, where they colocalize and cosegregate with syndecans. Cells that overexpress eGFP-syntenin show numerous cell surface extensions, suggesting effects of syntenin on cytoskeleton--membrane organization. We propose that syntenin may function as an adaptor that couples syndecans to cytoskeletal proteins or cytosolic downstream signal-effectors.