α-Klotho's effects on mineral homeostasis are fibroblast growth factor-23 dependent

Current Opinion in Nephrology and Hypertension
Reinhold G Erben

Abstract

α-Klotho (Klotho) occurs in three isoforms, a membrane-bound form acting as a coreceptor for fibroblast growth factor-23 (FGF23) signalling, a shed soluble form consisting of Klotho's large ectodomain thought to act as an enzyme or a hormone, and a secreted truncated form generated by alternative splicing of the Klotho mRNA with unknown function. The purpose of this review is to highlight the recent advances in our understanding of Klotho's function in mineral homeostasis. A number of seminal discoveries have recently been made in this area, shifting existing paradigms. The crystal structure of the ternary FGF receptor (FGFR)-1c/Klotho/FGF23 complex has been uncovered, revealing how the ligand FGF23 interacts with FGFR1c and the coreceptor Klotho at atomic resolution. Furthermore, it was shown that soluble Klotho lacks any glycosidase activity and serves as a bona fide coreceptor for FGF23 signalling. Experiments with a combination of Klotho and Fgf23-deficient mouse models demonstrated that all isoforms of Klotho lack any physiologically relevant, FGF23-independent functions in mineral homeostasis or ageing. Finally, it was demonstrated that the alternatively spliced Klotho mRNA is degraded and is not translated into a secrete...Continue Reading

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Citations

Mar 8, 2019·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Amin CheikhiFabrisia Ambrosio
Mar 25, 2020·Metabolites·Guido GembilloDomenico Santoro
Jul 28, 2019·Cellular and Molecular Life Sciences : CMLS·Edward R SmithTim D Hewitson
May 29, 2019·Current Opinion in Rheumatology·Susan M Ott

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Methods Mentioned

BETA
glycosylation

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