Clustering induces redistribution of syndecan-4 core protein into raft membrane domains.
Syndecan-4 is a heparan sulfate-carrying core protein that has been directly implicated in fibroblast growth factor 2 (FGF2) signaling. Recent studies have suggested that many signaling proteins localize to the raft compartment of the plasma cell membrane. To establish whether syndecan-4 is present in the raft compartment, we have studied the distribution of the core protein and an Fc receptor (FcR)-syndecan-4 chimera prior to and following clustering with FGF2 or antibodies. Whereas unclustered syndecan-4 was present predominantly in the non-raft membrane compartment, clustering induced extensive syndecan-4 redistribution to the rafts as demonstrated by the sucrose gradient centrifugation and life confocal microscopy. Although syndecan-4 and caveolin-1 moved in tandem, syndecan-4 was not present in caveolae, a major subset of raft compartments. We conclude that syndecan-4 clustering induces its redistribution to the non-caveolae raft compartment. This process may play an important role in syndecan-4-mediation of FGF2 signaling.
Tkachenko
Eugene
E
Angiogenesis Research Center and Section of Cardiology, Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
Simons
Michael
M
D000818:Animals; D019921:Biotinylation; D051242:Caveolin 1; D022461:Caveolins / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002469:Cell Separation; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D008562:Membrane Glycoproteins / Q000737:chemistry*; D021962:Membrane Microdomains / Q000737:chemistry* / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011233:Precipitin Tests; D011485:Protein Binding; D011509:Proteoglycans / Q000737:chemistry*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013395:Sucrose / Q000378:metabolism; D053671:Syndecan-4; D014162:Transfection
C495540:CAV1 protein, human; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; C508304:SDC4 protein, human; C508307:Sdc4 protein, rat; D053671:Syndecan-4; D016222:Fibroblast Growth Factor 2; D013395:Sucrose