Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 45, Pages 17532-17537Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0807413105
Keywords
envelope protein; human endogenous retrovirus (HERV); major facilitator superfamily domain containing 2 (MFSD2); syncytiotrophoblast
Categories
Funding
- Centre National de la Recherche Scientifique (CNRS)
- Ligue Nationale contre le Cancer
- CNRS
- Association pour la Recherche sur le Cancer
- Fondation pour la Recherche Medicale
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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.
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