Cell-cell fusion induced by the Ig3 domain of receptor FGFRL1 in CHO cells.

Zhuang, Lei; Pandey, Amit Vikram; Villiger, Peter; Trueb, Beat (2015). Cell-cell fusion induced by the Ig3 domain of receptor FGFRL1 in CHO cells. Biochimica et biophysica acta - molecular cell research, 1853(10 Pt A), pp. 2273-2285. Elsevier 10.1016/j.bbamcr.2015.05.027

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Tiefenau Hospital (discontinued) > Forschungsgruppe Endokrinologie/Diabetologie/Metabolik (Pädiatrie) (discontinued)

UniBE Contributor:

Zhuang, Lei; Pandey, Amit Vikram; Villiger, Peter and Trueb, Beat

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0167-4889

Publisher:

Elsevier

Language:

English

Submitter:

André Schaller

Date Deposited:

08 Apr 2016 10:15

Last Modified:

29 May 2017 17:49

Publisher DOI:

10.1016/j.bbamcr.2015.05.027

PubMed ID:

26025674

Uncontrolled Keywords:

Fibroblast growth factor (FGF); Fibroblast growth factor receptor (FGFR); Fusion protein; Fusogen; Molecular modeling; Syncytia

BORIS DOI:

10.7892/boris.79367

URI:

https://boris.unibe.ch/id/eprint/79367

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