Fusexins, a family of sexual, somatic and viral cell fusion proteins

MOI, DAVID; VALANSI, CLARI; ROMERO, HECTOR; PODBILEWICZ, BENJAMIN; LEIKINA, EUGENIA; AGUILAR, PABLO S

CABA

Congreso; Reunion Conjunta de Sociedades de Biociencias; 2017

SAIB, SAIC, SAB, SAI, SAFE, SAFIS, SAH, SAP, SAA

Cell-cell fusion is essential for fertilization and sculpting of bones, muscles, epidermis andplacenta in different organisms. However, the proteins that mediate membrane fusion betweencells have not yet been well-characterized and in some cases are still unknown. HAP2(GCS1) aremembrane glycoproteins essential for gamete fusion in plants, Chlamydomonas, Plasmodium,Tetrahymena, and Dictyostelium. To investigate whether HAP2 is not only essential but alsosufficient for cell-cell fusion, we expressed the Arabidopsis sperm HAP2 in cultured baby hamsterkidney cells that normally do not fuse. We found that HAP2 expression in these heterologouscells results in the formation of multinucleate cells by cell-to- cell fusion 1 . Genetic and cellbiological analyses showed that HAP2 has to be present in only one of the fusion partners(usually the male gamete) 2,3 . However, we found that when expressed in mammalian cells,Arabidopsis HAP2 is sufficient to fuse them only when expressed in both fusing cells 1 . Thus,HAP2-mediated plasma membrane merger occurs via a bilateral zippering mechanismreminiscent to intracellular fusions mediated by SNAREs, atlastins and mitofusins. Furthermore,expression of HAP2 on the surface of pseudotyped vesicular stomatitis virus results in virus-cellfusion only to cells that also express HAP2. Thus, we propose that, in addition to sperm HAP2, aHAP2-like protein is needed in the egg for gamete fusion. Structural modeling of the HAP2protein family predicts that it is homologous to class II viral fusion proteins (e.g. Zika, rubella anddengue) and the somatic cell fusogen EFF-1 from C. elegans 1-3 . Moreover, the recently solvedcrystal structure of Chlamydomonas? HAP2 demonstrates structural homology with EFF-1 andclass II viral fusion proteins 3 . We name this superfamily FUSEXINS: FUSion proteins essentialfor sexual reproduction and EXoplasmic merger of plasma membranes. Fusexins mediateenveloped virus entry into cells, sexual reproduction, and somatic cell fusion. These proteinsshare the same structure and function but use distinct mechanisms to merge membranes. Wehypothesize that modern fusexins have existed since the dawn of eukaryotic cells.