title: A novel human endogenous retroviral protein inhibits cell-cell fusion.
abstract: While common in viral infections and neoplasia, spontaneous cell-cell fusion, or syncytialization, is quite restricted in healthy tissues. Such fusion is essential to human placental development, where interactions between trophoblast-specific human endogenous retroviral (HERV) envelope proteins, called syncytins, and their widely-distributed cell surface receptors are centrally involved. We have identified the first host cell-encoded protein that inhibits cell fusion in mammals. Like the syncytins, this protein, called suppressyn, is HERV-derived, placenta-specific and well-conserved over simian evolution. In vitro, suppressyn binds to the syn1 receptor and inhibits syn1-, but not syn2-mediated trophoblast syncytialization. Suppressyn knock-down promotes cell-cell fusion in trophoblast cells and cell-associated and secreted suppressyn binds to the syn1 receptor, ASCT2. Identification of the first host cell-encoded inhibitor of mammalian cell fusion may encourage improved understanding of cell fusion mechanisms, of placental morphogenesis and of diseases resulting from abnormal cell fusion.
authors.affiliation: University of Missouri-Columbia, Department of Obstetrics, Gynecology and Women's Health, Division of Reproductive Endocrinology and Infertility, 500 North Keene Street, Columbia, MO 65201, USA. jsokiaji1@gmail.com
authors.forename: Jun
authors.initials: J
authors.lastname: Sugimoto
authors.forename: Makiko
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Helene
authors.initials: H
authors.lastname: Bernstein
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Jinno
authors.forename: Danny
authors.initials: D
authors.lastname: Schust
mesh_terms: D000595:Amino Acid Sequence; D026962:Amino Acid Transport System ASC / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002459:Cell Fusion; D002460:Cell Line; D045744:Cell Line, Tumor; D020077:Endogenous Retroviruses / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D026962:Amino Acid Transport System ASC; C583305:ERVH48-1 protein, human; D015686:Gene Products, env; D015778:Minor Histocompatibility Antigens; D011257:Pregnancy Proteins; C420506:SLC1A5 protein, human; D014759:Viral Envelope Proteins