title: ArabidopsisHAP2/GCS1 is a gamete fusion protein homologous to somatic and viral fusogens.
abstract: Cell-cell fusion is inherent to sexual reproduction. Loss of HAPLESS 2/GENERATIVE CELL SPECIFIC 1 (HAP2/GCS1) proteins results in gamete fusion failure in diverse organisms, but their exact role is unclear. In this study, we show thatArabidopsis thalianaHAP2/GCS1 is sufficient to promote mammalian cell-cell fusion. Hemifusion and complete fusion depend on HAP2/GCS1 presence in both fusing cells. Furthermore, expression of HAP2 on the surface of pseudotyped vesicular stomatitis virus results in homotypic virus-cell fusion. We demonstrate that theCaenorhabditis elegansEpithelial Fusion Failure 1 (EFF-1) somatic cell fusogen can replace HAP2/GCS1 in one of the fusing membranes, indicating that HAP2/GCS1 and EFF-1 share a similar fusion mechanism. Structural modeling of the HAP2/GCS1 protein family predicts that they are homologous to EFF-1 and viral class II fusion proteins (e.g., Zika virus). We name this superfamily Fusexins: fusion proteins essential for sexual reproduction and exoplasmic merger of plasma membranes. We suggest a common origin and evolution of sexual reproduction, enveloped virus entry into cells, and somatic cell fusion.
authors.affiliation: Department of Biology, Technion- Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Clari
authors.initials: C
authors.lastname: Valansi
authors.affiliation: Laboratorio de Biología Celular de Membranas, Instituto de Investigaciones Biotecnologicas "Dr. Rodolfo A. Ugalde," Universidad Nacional de San Martin, Buenos Aires, CP1650, Argentina.
authors.forename: David
authors.initials: D
authors.lastname: Moi
authors.affiliation: Section on Membrane Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Leikina
authors.affiliation: Department of Biology, Technion- Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Matveev
authors.affiliation: Unidad de Bioinformática, Institut Pasteur Montevideo, Montevideo 11400, Uruguay.
authors.forename: Martín
authors.identifier: 0000-0003-1182-8236
authors.initials: M
authors.lastname: Graña
authors.affiliation: Section on Membrane Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Leonid V
authors.initials: LV
authors.lastname: Chernomordik
authors.affiliation: Laboratorio de Organización y Evolución del Genoma, Unidad de Genómica Evolutiva, Departamento Ecología y Evolución, Facultad de Ciencias/Centro Universitario Regional del Este, Universidad de la República, Montevideo 11400, Uruguay.
authors.forename: Héctor
authors.identifier: 0000-0001-9685-0584
authors.initials: H
authors.lastname: Romero
authors.affiliation: Laboratorio de Biología Celular de Membranas, Instituto de Investigaciones Biotecnologicas "Dr. Rodolfo A. Ugalde," Universidad Nacional de San Martin, Buenos Aires, CP1650, Argentina paguilar@iib.unsam.edu.ar podbilew@technion.ac.il.
authors.forename: Pablo S
authors.initials: PS
authors.lastname: Aguilar
authors.affiliation: Department of Biology, Technion- Israel Institute of Technology, Haifa 32000, Israel paguilar@iib.unsam.edu.ar podbilew@technion.ac.il.
authors.forename: Benjamin
authors.identifier: 0000-0002-0411-4182
authors.initials: B
authors.lastname: Podbilewicz
mesh_terms: D000818:Animals; D017360:Arabidopsis / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002459:Cell Fusion / Q000379:methods; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D006224:Cricetinae; D005854:Germ Cells / Q000378:metabolism*; D008561:Membrane Fusion / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C470734:EFF-1 protein, C elegans; C548817:HAP2 protein, Arabidopsis; D008562:Membrane Glycoproteins; D014760:Viral Fusion Proteins