Syntenin, a PDZ protein that binds syndecan cytoplasmic domains

Syntenin, a PDZ protein that binds syndecan cytoplasmic domains

Laboratory for Glycobiology and Developmental Genetics, Center for Human Genetics, University of Leuven, and Flanders Interuniversity Institute for Biotechnology, 3000 Leuven, Belgium

Edited by Elizabeth D. Hay, Harvard Medical School, Boston, MA, and approved September 26, 1997 (received for review July 14, 1997)

Abstract

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.

Footnotes

↵ * J.J.G. and P.Z. contributed equally to this work.
↵ † To whom reprint requests should be addressed at: Center for Human Genetics, Campus Gasthuisberg, O&N, Herestraat 49, B-3000 Leuven, Belgium. e-mail: guido.david{at}med.kuleuven.ac.be.
This paper was submitted directly (Track II) to the Proceedings Office.
Abbreviations: eGFP, enhanced green fluorescent protein; FBS: fetal bovine serum; GST, glutathione S-transferase; PDZ, postsynaptic density protein, disc-large, zonulin-1; CHO, chinese hamster ovary.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF000652).