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Gewählte Publikation:

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Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2014

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

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

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



Autor/innen der Vetmeduni Vienna:

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

Beteiligte Vetmed-Organisationseinheiten
Institut für Physiologie, Pathophysiologie und Biophysik, Abteilung für Physiologie, Pathophysiologie und experimentelle Endokrinologie
Institut für Physiologie, Pathophysiologie und Biophysik, Abteilung für Physiologie und Biophysik
Institut für Morphologie


Zugehörige(s) Projekt(e): Vitamin D-unabhängige Funktion von Fgf23 und Klotho


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


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