title: Tyrosine dephosphorylation of the syndecan-1 PDZ binding domain regulates syntenin-1 recruitment.
abstract: Heparan sulfate proteoglycan receptor syndecan-1 interacts with the carboxyl-terminal LG4/5 domain in laminin 332 (alpha3LG4/5) and participates in cell adhesion and spreading. To dissect the function of syndecan-1 in these processes, we made use of a cell adhesion model in which syndecan-1 exclusively interacts with a recombinantly expressed alpha3LG4/5 fragment. Plating HT1080 cells on this fragment induces the formation of actin-containing protrusive structures in an integrin-independent manner. Here we show that syndecan-1-mediated formation of membrane protrusions requires dephosphorylation of tyrosine residues in syndecan-1. Accordingly, inhibition of phosphatases with orthovanadate decreases cell adhesion to the alpha3LG4/5 fragment. We demonstrate that the PDZ-containing protein syntenin-1, known to connect cytoskeletal proteins, binds to syndecan-1 in cells plated on the alpha3LG4/5 fragment and participates in the formation of membrane protrusions. We further show that syntenin-1 recruitment depends on the dephosphorylation of Tyr-309 located within syndecan-1 PDZ binding domain EFYA. We propose that tyrosine dephosphorylation of syndecan-1 may regulate its association with cytoskeleton components.
authors.affiliation: IFR128 BioSciences Gerland-Lyon Sud, Institut de Biologie et Chimie des Protéines, UMR 5086, CNRS, Université Lyon1, 7 passage du Vercors, 69367 Lyon, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Sulka
authors.forename: Hugues
authors.initials: H
authors.lastname: Lortat-Jacob
authors.forename: Raphael
authors.initials: R
authors.lastname: Terreux
authors.forename: François
authors.initials: F
authors.lastname: Letourneur
authors.forename: Patricia
authors.initials: P
authors.lastname: Rousselle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D022081:Cell Surface Extensions / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D053668:Syndecan-1 / Q000235:genetics / Q000378:metabolism*; D053676:Syntenins / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D053668:Syndecan-1; D053676:Syntenins; D014443:Tyrosine