The Cooperation of FGF receptor and Klotho is involved in Excretory Canal Development and Regulation of Metabolic Homeostasis in Caenorhabditis elegans

Urszula M. Polanska, Elisabeth Edwards, David G. Fernig, Tarja K. Kinnunen

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5657-5666
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number7
Early online date21 Dec 2010
DOIs
Publication statusPublished - 18 Feb 2011
Externally publishedYes

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Fibroblast Growth Factor Receptors
Caenorhabditis elegans
Canals
Homeostasis
Aging of materials
Premature Aging
Kidney
Mammals
Cell proliferation
Medical problems
Energy balance
Morphogenesis
Metabolism
Vitamin D
Vertebrates
Genes
Phosphates
Cell Proliferation
Genome
Hormones

Cite this

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title = "The Cooperation of FGF receptor and Klotho is involved in Excretory Canal Development and Regulation of Metabolic Homeostasis in Caenorhabditis elegans",
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.",
keywords = "Aging, C.elegans, Growth Factors, Kidney, Metabolic Regulation, Signal Transduction, FGF, Kiotho, Endocrine",
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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, Urszula M.; Edwards, Elisabeth; Fernig, David G.; Kinnunen, Tarja K.

In: Journal of Biological Chemistry, Vol. 286, No. 7, 18.02.2011, p. 5657-5666.

Research output: Contribution to journalArticle

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T1 - The Cooperation of FGF receptor and Klotho is involved in Excretory Canal Development and Regulation of Metabolic Homeostasis in Caenorhabditis elegans

AU - Polanska, Urszula M.

AU - Edwards, Elisabeth

AU - Fernig, David G.

AU - Kinnunen, Tarja K.

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KW - C.elegans

KW - Growth Factors

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KW - FGF

KW - Kiotho

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U2 - 10.1074/jbc.M110.173039

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JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

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