HGNC Approved Gene Symbol: FGFRL1
Cytogenetic location: 4p16.3 Genomic coordinates (GRCh38) : 4:1,010,212-1,026,898 (from NCBI)
Fibroblast growth factor receptors (FGFRs) are members of the receptor tyrosine kinase family that are activated by interaction with FGFs. See FGFR2 (176943) and FGF12 (601513) for additional information on FGFRs and FGFs.
Using a subtractive cDNA cloning approach to identify cartilage-specific proteins, Wiedemann and Trueb (2000) identified FGFRL1. Using sequence analysis, they predicted that the FGFRL1 gene contains 6 exons encoding a deduced 504-amino acid protein with a molecular mass of 55 kD and an isoelectric point of 10.6. FGFRL1 contains a predicted signal peptide and transmembrane domain. Similarity to other FGFRs is restricted to the extracellular immunoglobulin domains and the transmembrane domain. Wiedemann and Trueb (2000) hypothesized that FGFRL1 is a member of the FGFR family that lacks a cytoplasmic protein tyrosine kinase domain. Northern blot analysis detected preferential expression of a 3.4-kb FGFRL1 transcript in cartilage-containing fetal tissues including vertebrae, bone, and total embryo. Weak expression was also detected in fetal muscle.
Steinberg et al. (2010) stated that human FGFRL1 has 3 N-terminal Ig-like domains, followed by a transmembrane domain, a double-tyrosine (YY) motif, and a histidine-rich C-terminal domain.
Steinberg et al. (2010) found that expression of human FGFRL1 in Chinese hamster ovary (CHO) cells induced extensive fusion of CHO cells into large multinuclear syncitia. Nontransfected CHO cells also fused with other FGFRL1-transfected cell lines, including HEK293 and HeLa cells, but FGFRL1 did not induce fusion in any cell line in the absence of CHO cells. Steinberg et al. (2010) were unable to determine the critical factor present in CHO cells that permitted cell fusion. Mutation analysis revealed that Ig-like domain III and the transmembrane domain of FGFRL1 were necessary and sufficient for its fusigenic activity. The cytoplasmic C-terminal domain mediated internalization of FGFRL1, and deletion of the C-terminal domain increased the surface expression of FGFRL1 and thereby increased the extent of cell fusion. Inhibitor studies showed that polymerization of the actin cytoskeleton, but not tubulin, was required for FGFRL1-induced fusion. Interaction of FGFRL1 with cell surface heparin sulfates inhibited FGFRL1-induced cell fusion.
By fluorescence in situ hybridization, Wiedemann and Trueb (2000) mapped the FGFRL1 gene to chromosome 4p16 in close proximity to the FGFR3 (134934) gene.
Steinberg, F., Gerber, S. D., Rieckmann, T., Trueb, B. Rapid fusion and syncytium formation of heterologous cells upon expression of the FGFRL1 receptor. J. Biol. Chem. 285: 37704-37715, 2010. [PubMed: 20851884] [Full Text: https://doi.org/10.1074/jbc.M110.140517]
Wiedemann, M., Trueb, B. Characterization of a novel protein (FGFRL1) from human cartilage related to FGF receptors. Genomics 69: 275-279, 2000. [PubMed: 11031111] [Full Text: https://doi.org/10.1006/geno.2000.6332]