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The Cooperation of FGF Receptor and Klotho Is Involved in Excretory Canal Development and Regulation of Metabolic Homeostasis in Caenorhabditis elegans

Polanska, U. M., Edwards, E., Fernig, D. G. and Kinnunen, Tarja (2011) The Cooperation of FGF Receptor and Klotho Is Involved in Excretory Canal Development and Regulation of Metabolic Homeostasis in Caenorhabditis elegans. Journal of Biological Chemistry, 286 (7). pp. 5657-5666. ISSN 0021-9258

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Abstract

FGFs have traditionally been associated with cell proliferation, morphogenesis, and development; yet, a subfamily of FGFs (FGF19, -21, and -23) functions as hormones to regulate glucose, lipid, phosphate, and vitamin D metabolism with impact on energy balance and aging. In mammals, Klotho and beta-Klotho are type 1 transmembrane proteins that function as obligatory co-factors for endocrine FGFs to bind to their cognate FGF receptors (FGFRs). Mutations in Klotho/beta-Klotho or fgf19, -21, or -23 are associated with a number of human diseases, including autosomal dominant hypophosphatemic rickets, premature aging disorders, and diabetes. The Caenorhabditis elegans genome contains two paralogues of Klotho/beta-Klotho, klo-1, and klo-2. klo-1 is expressed in the C. elegans excretory canal, which is structurally and functionally paralogous to the vertebrate kidney. KLO-1 associates with EGL-15/FGFR, suggesting a role for KLO-1 in the fluid homeostasis phenotype described previously for egl-15/fgfr mutants. Altered levels of EGL-15/FGFR signaling lead to defects in excretory canal development and function in C. elegans. These results suggest an evolutionarily conserved function for the FGFR-Klotho complex in the development of excretory organs such as the mammalian kidney and the worm excretory canal. These results also suggest an evolutionarily conserved function for the FGFR-Klotho axis in metabolic regulation.

Item Type: Article
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
Schools: School of Applied Sciences
Depositing User: Sara Taylor
Date Deposited: 13 Dec 2012 15:27
Last Modified: 13 Dec 2012 15:27
URI: http://eprints.hud.ac.uk/id/eprint/16350

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