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Type of publication: Journal Article
Type of document: Full Paper

Year: 2014

Authors: Andrukhova, O; Smorodchenko, A; Egerbacher, M; Streicher, C; Zeitz, U; Goetz, R; Shalhoub, V; Mohammadi, M; Pohl, EE; Lanske, B; Erben, RG

Title: FGF23 promotes renal calcium reabsorption through the TRPV5 channel.

Source: EMBO J. 2014; 33(3):229-246

Authors Vetmeduni Vienna:

Andrukhova Olena
Egerbacher Monika
Erben Reinhold
Pohl Elena
Smorodchenko Alina
Streicher Carmen
Zeitz Ute

Vetmed Research Units
Institute of Morphology
Institute of Physiology, Pathohysiology and Biophysics, Unit of Physiology and Biophysics
Institute of Physiology, Pathohysiology and Biophysics, Unit of Physiology, Pathophysiology, and Experimental Endocrinology

Project(s): Vitamin D-unabhängige Funktion von Fgf23 und Klotho

αKlotho is thought to activate the epithelial calcium channel Transient Receptor Potential Vanilloid-5 (TRPV5) in distal renal tubules through its putative glucuronidase/sialidase activity, thereby preventing renal calcium loss. However, αKlotho also functions as the obligatory co-receptor for fibroblast growth factor-23 (FGF23), a bone-derived phosphaturic hormone. Here, we show that renal calcium reabsorption and renal membrane abundance of TRPV5 are reduced in Fgf23 knockout mice, similar to what is seen in αKlotho knockout mice. We further demonstrate that αKlotho neither co-localizes with TRPV5 nor is regulated by FGF23. Rather, apical membrane abundance of TRPV5 in renal distal tubules and thus renal calcium reabsorption are regulated by FGF23, which binds the FGF receptor-αKlotho complex and activates a signaling cascade involving ERK1/2, SGK1, and WNK4. Our data thereby identify FGF23, not αKlotho, as a calcium-conserving hormone in the kidney.

Keywords Pubmed: Animals
Cell Membrane/metabolism
Fibroblast Growth Factors/genetics
Fibroblast Growth Factors/metabolism*
Immediate-Early Proteins/metabolism
Mice, Knockout
Protein-Serine-Threonine Kinases/metabolism
Receptors, Cell Surface/metabolism*
Signal Transduction
TRPV Cation Channels/metabolism*

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