title: Syndecan-2 expression increases serum-withdrawal-induced apoptosis, mediated by re-distribution of Fas into lipid rafts, in stably transfected Swiss 3T3 cells.
abstract: To examine the function of syndecan-2, one of the most abundant heparan sulfate proteoglycans in fibroblasts, we obtained stably transfected Swiss 3T3 clones. We examined the effects of stable syndecan-2 overexpression on programmed cell death, finding that syndecan-2 transfected cells were more sensitive to apoptosis induced by serum-withdrawal than control cells. In addition, overexpression of syndecan-2 correlates with increased membrane levels of the Fas/CD95 receptor, suggesting that the increased serum-withdrawal apoptosis observed in Swiss 3T3 cells might be Fas receptor-dependent. Differences in Fas membrane levels between both control and syndecan-2 transfected cells result from a redistribution of the Fas receptor. Our data clearly demonstrate that increased Fas levels are primarily related to lipid rafts and that this increase is a key factor in Fas/CD95-mediated apoptosis. Moreover, disruption of lipid rafts with methyl-beta-cyclodextrin or filipin significantly reduced apoptosis in response to serum withdrawal. The differences in Fas/CD95 membrane distribution could explain why syndecan-2 transfected cells have a higher susceptibility to serum-withdrawal-induced apoptosis.
authors.affiliation: Department of Cellular Biology, Faculty of Biology, University of Barcelona, Diagonal 645, 08028, Barcelona, Spain. juan.villena@uv.cl
authors.forename: Joan
authors.initials: J
authors.lastname: Villena
authors.forename: Jessica
authors.initials: J
authors.lastname: Mainez
authors.forename: Oriol
authors.initials: O
authors.lastname: Noguer
authors.forename: Héctor
authors.initials: H
authors.lastname: Contreras
authors.forename: Francesc
authors.initials: F
authors.lastname: Granés
authors.forename: Manuel
authors.initials: M
authors.lastname: Reina
authors.forename: Isabel
authors.initials: I
authors.lastname: Fabregat
authors.forename: Senén
authors.initials: S
authors.lastname: Vilaró
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D018929:Cell Culture Techniques; D018076:DNA, Complementary; D004285:Dogs; D053222:Fas Ligand Protein / Q000378:metabolism*; D005372:Filipin / Q000494:pharmacology; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D044967:Serum / Q000378:metabolism*; D053669:Syndecan-2 / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D018076:DNA, Complementary; D053222:Fas Ligand Protein; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D053669:Syndecan-2; D005372:Filipin