RT Journal Article SR Electronic T1 Arabidopsis HAP2/GCS1 is a gamete fusion protein homologous to somatic and viral fusogens JF bioRxiv FD Cold Spring Harbor Laboratory SP 097568 DO 10.1101/097568 A1 Clari Valansi A1 David Moi A1 Evgenia Leikina A1 Elena Matveev A1 Martín Graña A1 Leonid V Chernomordik A1 Héctor Romero A1 Pablo S. Aguilar A1 Benjamin Podbilewicz YR 2016 UL http://biorxiv.org/content/early/2016/12/31/097568.abstract AB Cell-cell fusion is inherent to any form of sexual reproduction. Loss of HAPLESS 2/GENERATIVE CELL SPECIFIC 1 (HAP2/GCS1) proteins results in gamete fusion failure in different organisms but their exact role is unclear. Here we show that Arabidopsis HAP2/GCS1 expression in mammalian cells is sufficient to promote 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 and on the target cells results in HAP2-dependent virus-cell fusion. This bilateral requirement can be bypassed by replacing the plant gene with C. elegans EFF-1 somatic cell fusogen in one of the fusing cells or the virus, 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 class II fusion proteins from enveloped viruses (e.g. dengue and Zika viruses). We name this superfamily FUSEXINS: FUSion proteins essential for sexual reproduction and EXoplasmic merger of plasma membranes. Thus, Fusexins unify the origin and evolution of sexual reproduction, enveloped virus entry into cells and somatic cell fusion.AtHAP2Arabidopsis thaliana HAP2BHKBaby Hamster Kidney cellsEFF-1Epithelial Fusion Failure 2FUSEXINSFUSion proteins essential for sexual reproduction and EXoplasmic merger of plasma membranesGCS1Generative Cell Specific 1HAP2Happless 2HMMshidden Markov ModelsVSVVesicular Stomatitis VirusVSVΔGVSV pseudoviruses in which the glycoprotein G gene was deleted