title: C-Terminal truncations of syncytin-1 (ERVWE1 envelope) that increase its fusogenicity.
abstract: Syncytin-1, the envelope protein of ERVWE1, an endogenous retrovirus of the HERV-W family, plays an important role in regulating fusion of the placental trophoblast. At least one of its receptors is expressed on a variety of human cell types. Its ability to fuse cells makes it an attractive candidate molecule in gene therapy against cancer. We studied the relevance of sequences in the cytoplasmic tail of syncytin-1 for inducing cell-cell fusion. We generated a series of C-terminally truncated syncytin-1 variants. Sequences immediately adjacent to the transmembrane region of syncytin-1 were necessary for inducing optimal fusion, whereas the extreme C-terminus of syncytin-1 partially inhibited its fusogenicity. Two variants of syncytin-1, truncated after residues 483 and 515, were significantly hyperfusogenic compared to wild-type syncytin-1. Cellular and cell-surface expression levels of these two variant proteins were similar to those of wild-type syncytin-1. In testing the latter we found that only a very minor portion of recombinantly expressed cellular syncytin-1 was fully mature and expressed on the cell surface. Our results contribute to the understanding of the structure-function relationship of syncytin-1, and might have implications for the use of this molecule in gene therapy.
authors.affiliation: Institute of Anatomy II, University Hospital, Wendlingweg 2, RWTH Aachen, D-52057 Aachen, Germany. sdrewlo@ukaachen.de
authors.forename: Sascha
authors.initials: S
authors.lastname: Drewlo
authors.forename: Simone
authors.initials: S
authors.lastname: Leyting
authors.forename: Maria
authors.initials: M
authors.lastname: Kokozidou
authors.forename: François
authors.initials: F
authors.lastname: Mallet
authors.forename: Andy J G
authors.initials: AJ
authors.lastname: Pötgens
mesh_terms: D000818:Animals; D019921:Biotinylation; D015153:Blotting, Western; D016466:CHO Cells; D002457:Cell Extracts / Q000737:chemistry; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D005786:Gene Expression Regulation / Q000235:genetics; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D014644:Genetic Variation; D006801:Humans; D011257:Pregnancy Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013499:Surface Properties
chemical_list: D002457:Cell Extracts; D015686:Gene Products, env; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C405335:syncytin