title: A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2.
abstract: Syncytin-2 is an envelope gene from the human endogenous retrovirus FRD (HERV-FRD) co-opted by an ancestral primate host, conserved in evolution over >40 Myr, specifically expressed in the placenta, and with a cell-cell fusogenic activity likely contributing to placenta morphogenesis. Here, using the GeneBridge4 human/Chinese hamster radiation hybrid panel, we mapped and identified the human receptor for syncytin-2. This receptor-namely Major Facilitator Superfamily Domain Containing 2 (MFSD2)-belongs to a large family of presumptive carbohydrate transporters with 10-12 membrane-spanning domains, is located at chromosomal position 1p34.2, and is conserved in evolution. An expression vector for MFSD2 confers fusogenicity to otherwise insusceptible cells upon transfection of syncytin-2. It also confers infectivity to syncytin-2 pseudotypes, consistent with this protein being the receptor for the ancestrally acquired HERV-FRD family of endogenous retroviruses. At variance with the human gene, neither mouse nor rat MFSD2 can mediate membrane fusion, which is consistent with the fact that the envelope-derived syncytin genes co-opted by rodents during evolution are not orthologous to the human syncytin genes. Remarkably, a real-time quantitative RT-PCR analysis of MFSD2 in various human tissues demonstrates specific expression in the placenta, as well as in the human BeWo choriocarcinoma cell line, which discloses enhancement of receptor expression upon induction by forskolin of cell-cell fusion and syncytium formation. In situ hybridization of human placental tissue using an MFSD2-specific probe further unambiguously demonstrates receptor expression at the level of the syncytiotrophoblast, again consistent with a role in placenta morphogenesis.
authors.affiliation: Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8122, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Esnault
authors.forename: Stéphane
authors.initials: S
authors.lastname: Priet
authors.forename: David
authors.initials: D
authors.lastname: Ribet
authors.forename: Cécile
authors.initials: C
authors.lastname: Vernochet
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruls
authors.forename: Christian
authors.initials: C
authors.lastname: Lavialle
authors.forename: Jean
authors.initials: J
authors.lastname: Weissenbach
authors.forename: Thierry
authors.initials: T
authors.lastname: Heidmann
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D010920:Placenta / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics; D021101:Radiation Hybrid Mapping; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C518353:ERVFRD-1 protein, human; C533865:MFSDC2 protein, human; D008565:Membrane Proteins; D011257:Pregnancy Proteins