title: The oligomeric status of syndecan-4 regulates syndecan-4 interaction with alpha-actinin.
abstract: Syndecan-4, a cell surface heparan sulfate proteoglycan, is known to regulate the organization of the cytoskeleton, and oligomerization is crucial for syndecan-4 function. We therefore explored a possible regulatory effect of syndecan-4 oligomerization on the cytoskeleton. Glutathione-S-transferase-syndecan-4 proteins were used to show that syndecan-4 interacted specifically with alpha-actinin, but not paxillin, talin, and vinculin. Interestingly, only dimeric, and not monomeric, recombinant syndecan-4 interacted with alpha-actinin in the presence of phosphatidylinositol 4,5-bisphosphate (PIP2), and PIP2 potentiated the interaction of both the cytoplasmic domain syndecan-4 peptide and recombinant syndecan-4 proteins with alpha-actinin, implying that oligomerization of syndecan-4 was important for this interaction. Consistent with this notion, alpha-actinin interaction was largely absent in syndecan-4 mutants defective in transmembrane domain-induced oligomerization, and alpha-actinin-associated focal adhesions were decreased in rat embryo fibroblasts expressing mutant syndecan-4. Besides, this interaction was consistently lower with the phosphorylation-mimicking syndecan-4 mutant S183E which is known to destabilize the oligomerization of the syndecan-4 cytoplasmic domain. Taken together, the data suggest that the oligomeric status of syndecan-4 plays a crucial role in regulating the interaction of syndecan-4 with alpha-actinin.
authors.affiliation: Department of Life Sciences, Ewha Womans University, Daehyun-dong, Seodaemoon-Gu, Seoul 120-750, Korea.
authors.forename: Youngsil
authors.initials: Y
authors.lastname: Choi
authors.forename: Seungin
authors.initials: S
authors.lastname: Kim
authors.forename: Junghyun
authors.initials: J
authors.lastname: Lee
authors.forename: Sung-Gun
authors.initials: SG
authors.lastname: Ko
authors.forename: Weontae
authors.initials: W
authors.lastname: Lee
authors.forename: Inn-Oc
authors.initials: IO
authors.lastname: Han
authors.forename: Anne
authors.initials: A
authors.lastname: Woods
authors.forename: Eok-Soo
authors.initials: ES
authors.lastname: Oh
mesh_terms: D000185:Actinin / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D051381:Rats; D053671:Syndecan-4 / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D053671:Syndecan-4; D000185:Actinin