title: Selective activation of TACI by syndecan-2.
abstract: B-lymphocyte homeostasis and function are regulated by complementary actions of the TNFR family members TACI, BCMA, and BAFF-R, which are expressed by mature B cells. How these receptors are differentially activated is not entirely understood, because the primary ligand BAFF binds to all three. We searched for alternative ligands for TACI using recombinant TACI-Fc fusion protein as a probe and identified syndecan-2 as a new binding partner. TACI binding appears to require heparan sulfate posttranslational modifications of syndecan-2, because free heparin or pretreatment with heparitinase blocked the interaction. Syndecan-2 bound TACI but bound neither BAFF-R nor BCMA. Transfected cells expressing syndecan-2 activated signaling through TACI, as indicated by an NFAT-specific reporter. Syndecan-1 and syndecan-4 were also able to induce TACI signaling in a similar manner. This is the first identification of ligands that selectively activate TACI without simultaneously triggering BCMA or BAFF-R. This finding may help explain the alternative outcomes of signaling from this family of receptors in B cells.
authors.affiliation: Mayo Clinic, Mayo Medical School, Department of Pediatric and Adolescent Medicine, Rochester, MN 55905, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bischof
authors.forename: Sherine F
authors.initials: SF
authors.lastname: Elsawa
authors.forename: George
authors.initials: G
authors.lastname: Mantchev
authors.forename: Juhan
authors.initials: J
authors.lastname: Yoon
authors.forename: Grace E
authors.initials: GE
authors.lastname: Michels
authors.forename: Allan
authors.initials: A
authors.lastname: Nilson
authors.forename: Shari L
authors.initials: SL
authors.lastname: Sutor
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Platt
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.forename: Gotz
authors.initials: G
authors.lastname: von Bulow
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bram
mesh_terms: D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000276:immunology; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D053668:Syndecan-1; D053669:Syndecan-2; D053671:Syndecan-4; D053667:Syndecans; D014162:Transfection; D053303:Transmembrane Activator and CAML Interactor Protein
chemical_list: D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D011509:Proteoglycans; D018124:Receptors, Tumor Necrosis Factor; C508241:SDC1 protein, human; C508245:SDC2 protein, human; C508304:SDC4 protein, human; D053668:Syndecan-1; D053671:Syndecan-4; D053667:Syndecans; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; C086966:TNFRSF17 protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053669:Syndecan-2