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.
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Bioscience Building, Crown Street, Liverpool L69 7ZB, United Kingdom.
authors.forename: Urszula M
authors.initials: UM
authors.lastname: Polanska
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Edwards
authors.forename: David G
authors.initials: DG
authors.lastname: Fernig
authors.forename: Tarja K
authors.initials: TK
authors.lastname: Kinnunen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D000090265:Klotho Proteins; D009154:Mutation; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C112493:EGL-15 protein, C elegans; D017468:Receptors, Fibroblast Growth Factor; D005966:Glucuronidase; D000090265:Klotho Proteins