Evidence that the novel receptor FGFRL1 signals indirectly via FGFR1

Amann,Ruth; Trueb,Beat

doi:10.3892/ijmm.2013.1484

Evidence that the novel receptor FGFRL1 signals indirectly via FGFR1

Authors:
- Ruth Amann
- Beat Trueb
View Affiliations

Affiliations: Department of Clinical Research, University of Bern, 3010 Bern, Switzerland
Published online on: September 10, 2013 https://doi.org/10.3892/ijmm.2013.1484
Pages: 983-988
Copyright: © Amann et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Fibroblast growth factor (FGF) receptor-like protein 1 (FGFRL1) is a recently discovered member of the FGF receptor (FGFR) family. Similar to the classical FGFRs, it contains three extracellular immunoglobulin‑like domains and interacts with FGF ligands. However, in contrast to the classical receptors, it does not contain any intracellular tyrosine kinase domain and consequently cannot signal by transphosphorylation. In mouse kidneys, FgfrL1 is expressed primarily at embryonic stages E14-E15 in regions where nascent nephrons develop. In this study, we used whole-mount in situ hybridization to show the spatial pattern of five different Fgfrs in the developing mouse kidney. We compared the expression pattern of FgfrL1 with that of other Fgfrs. The expression pattern of FgfrL1 closely resembled that of Fgfr1, but clearly differed from that of Fgfr2‑Fgfr4. It is therefore conceivable that FgfrL1 signals indirectly via Fgfr1. The mechanisms by which FgfrL1 affects the activity of Fgfr1 remain to be elucidated.

View Figures

View References

1	Itoh N: The Fgf families in humans, mice, and zebrafish: their evolutional processes and roles in development, metabolism, and disease. Biol Pharm Bull. 30:1819–1825. 2007. View Article : Google Scholar : PubMed/NCBI
2	Beenken A and Mohammadi M: The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov. 8:235–253. 2009. View Article : Google Scholar : PubMed/NCBI
3	Costantini F and Kopan R: Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev Cell. 18:698–712. 2010. View Article : Google Scholar : PubMed/NCBI
4	Hendry C, Rumballe B, Moritz K and Little MH: Defining and redefining the nephron progenitor population. Pediatr Nephrol. 26:1395–1406. 2011. View Article : Google Scholar : PubMed/NCBI
5	Brown AC, Adams D, de Caestecker M, Yang X, Friesel R and Oxburgh L: FGF/EGF signaling regulates the renewal of early nephron progenitors during embryonic development. Development. 138:5099–5112. 2011. View Article : Google Scholar : PubMed/NCBI
6	Wiedemann M and Trueb B: Characterization of a novel protein (FGFRL1) from human cartilage related to FGF receptors. Genomics. 69:275–279. 2000. View Article : Google Scholar : PubMed/NCBI
7	Trueb B, Zhuang L, Taeschler S and Wiedemann M: Characterization of FGFRL1, a novel FGF receptor preferentially expressed in skeletal tissues. J Biol Chem. 278:33857–33865. 2003. View Article : Google Scholar : PubMed/NCBI
8	Sleeman M, Fraser J, McDonald M, Yuan S, White D, Grandison P, Kumble K, Watson JD and Murison JG: Identification of a new fibroblast growth factor receptor, FGFR5. Gene. 271:171–182. 2001. View Article : Google Scholar : PubMed/NCBI
9	Wiedemann M and Trueb B: The mouse Fgfrl1 gene coding for a novel FGF receptor–like protein. Biochim Biophys Acta. 1520:247–250. 2001.PubMed/NCBI
10	Trueb B: Biology of FGFRL1, the fifth fibroblast growth factor receptor. Cell Mol Life Sci. 68:951–964. 2011. View Article : Google Scholar : PubMed/NCBI
11	Baertschi S, Zhuang L and Trueb B: Mice with a targeted disruption of the FgfrL1 gene die at birth due to alterations in the diaphragm. FEBS J. 274:6241–6253. 2007. View Article : Google Scholar : PubMed/NCBI
12	Catela C, Bilbao-Cortes D, Slonimsky E, Kratsios P, Rosenthal N and Te Welscher P: Multiple congenital malformations of Wolf-Hirschhorn syndrome are recapitulated in Fgfrl1 null mice. Dis Model Mech. 2:283–294. 2009. View Article : Google Scholar : PubMed/NCBI
13	Gerber SD, Steinberg F, Beyeler M, Villiger PM and Trueb B: The murine FgfrL1 receptor is essential for the development of the metanephric kidney. Dev Biol. 335:106–119. 2009. View Article : Google Scholar : PubMed/NCBI
14	Gerber SD, Amann R, Wyder S and Trueb B: Comparison of the gene expression profiles from normal and FgfrL1 deficient mouse kidneys reveals downstream targets of FgfrL1 signaling. PLoS One. 7:e334572012. View Article : Google Scholar : PubMed/NCBI
15	Trueb B, Amann R and Gerber SD: Role of FGFRL1 and other FGF signaling proteins in early kidney development. Cell Mol Life Sci. 70:2505–2518. 2013. View Article : Google Scholar : PubMed/NCBI
16	Steinberg F, Zhuang L, Beyeler M, Kälin RE, Mullis PE, Brändli AW and Trueb B: The FGFRL1 receptor is shed from cell membranes, binds fibroblast growth factors (FGFs) and antagonizes FGF signaling in Xenopus embryos. J Biol Chem. 285:2193–2202. 2010. View Article : Google Scholar : PubMed/NCBI
17	Grieshammer U, Cebrian C, Ilagan R, Meyers E, Herzlinger D and Martin GR: FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons. Development. 132:3847–3857. 2005. View Article : Google Scholar : PubMed/NCBI
18	Perantoni AO, Timofeeva O, Naillat F, Richman C, Pajni-Underwood S, Wilson C, Vainio S, Dove LF and Lewandoski M: Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development. Development. 132:3859–3871. 2005. View Article : Google Scholar : PubMed/NCBI
19	Colvin JS, Bohne BA, Harding GW, McEwen DG and Ornitz DM: Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3. Nat Genet. 12:390–397. 1996. View Article : Google Scholar : PubMed/NCBI
20	Weinstein M, Xu X, Ohyama K and Deng CX: FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the murine lung. Development. 125:3615–3623. 1998.PubMed/NCBI
21	Deng CX, Wynshaw-Boris A, Shen MM, Daugherty C, Ornitz DM and Leder P: Murine FGFR-1 is required for early postimplantation growth and axial organization. Genes Dev. 8:3045–3057. 1994. View Article : Google Scholar : PubMed/NCBI
22	Yamaguchi TP, Harpal K, Henkemeyer M and Rossant J: Fgfr-1 is required for embryonic growth and mesodermal patterning during mouse gastrulation. Genes Dev. 8:3032–3044. 1994. View Article : Google Scholar : PubMed/NCBI
23	Xu X, Weinstein M, Li C, Naski M, Cohen RI, Ornitz DM, Leder P and Deng C: Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development. 125:753–765. 1998.PubMed/NCBI
24	Arman E, Haffner-Krausz R, Chen Y, Heath JK and Lonai P: Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development. Proc Natl Acad Sci USA. 95:5082–5087. 1998. View Article : Google Scholar : PubMed/NCBI
25	Poladia DP, Kish K, Kutay B, Hains D, Kegg H, Zhao H and Bates CM: Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme. Dev Biol. 291:325–339. 2006. View Article : Google Scholar : PubMed/NCBI
26	Zhao H, Kegg H, Grady S, Truong HT, Robinson ML, Baum M and Bates CM: Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. Dev Biol. 276:403–415. 2004. View Article : Google Scholar : PubMed/NCBI
27	Bates CM: Role of fibroblast growth factor receptor signaling in kidney development. Am J Physiol Renal Physiol. 301:F245–F251. 2011. View Article : Google Scholar : PubMed/NCBI
28	Rieckmann T, Kotevic I and Trueb B: The cell surface receptor FGFRL1 forms constitutive dimers that promote cell adhesion. Exp Cell Res. 314:1071–1081. 2008. View Article : Google Scholar : PubMed/NCBI
29	Steinberg F, Gerber S, Rieckmann T and Trueb B: Rapid fusion and syncytium formation of heterologous cells upon expression of the FGFRL1 receptor. J Biol Chem. 285:37704–37715. 2010. View Article : Google Scholar : PubMed/NCBI