title: Cell-cell fusion induced by the Ig3 domain of receptor FGFRL1 in CHO cells.
abstract: FGFRL1 is a single-pass transmembrane protein with three extracellular Ig domains. When overexpressed in CHO cells or related cell types, it induces cell-cell fusion and formation of large, multinucleated syncytia. For this fusion-promoting activity, only the membrane-proximal Ig domain (Ig3) and the transmembrane domain are required. It does not matter whether the transmembrane domain is derived from FGFRL1 or from another receptor, but the distance of the Ig3 domain to the membrane is crucial. Fusion can be inhibited with soluble recombinant proteins comprising the Ig1-Ig2-Ig3 or the Ig2-Ig3 domains as well as with monoclonal antibodies directed against Ig3. Mutational analysis reveals a hydrophobic site in Ig3 that is required for fusion. If a single amino acid from this site is mutated, fusion is abolished. The site is located on a β-sheet, which is part of a larger β-barrel, as predicted by computer modeling of the 3D structure of FGFRL1. It is possible that this site interacts with a target protein of neighboring cells to trigger cell-cell fusion.
authors.affiliation: Department of Clinical Research, University of Bern, 3010 Bern, Switzerland.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhuang
authors.affiliation: Department of Clinical Research, University of Bern, 3010 Bern, Switzerland; Department of Pediatric Endocrinology, University Children's Hospital, 3010 Bern, Switzerland.
authors.forename: Amit V
authors.initials: AV
authors.lastname: Pandey
authors.affiliation: Department of Rheumatology, University Hospital, 3010 Bern, Switzerland.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Villiger
authors.affiliation: Department of Clinical Research, University of Bern, 3010 Bern, Switzerland; Department of Rheumatology, University Hospital, 3010 Bern, Switzerland. Electronic address: beat.trueb@dkf.unibe.ch.
authors.forename: Beat
authors.initials: B
authors.lastname: Trueb
mesh_terms: D000818:Animals; D016466:CHO Cells; D002459:Cell Fusion; D006224:Cricetinae; D003412:Cricetulus; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051500:Receptor, Fibroblast Growth Factor, Type 5 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C417531:FGFRL1 protein, human; D051500:Receptor, Fibroblast Growth Factor, Type 5; D011994:Recombinant Proteins
keywords: Fibroblast growth factor (FGF); Fibroblast growth factor receptor (FGFR); Fusion protein; Fusogen; Molecular modeling; Syncytia