FGF23 Promotes Renal Calcium Reabsorption Through the TRPV5 Channel

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2014 Jan 18

PMID 24434184

Citations 101

Authors

Olena Andrukhova

Alina Smorodchenko

Monika Egerbacher

Carmen Streicher

Ute Zeitz

Regina Goetz

Victoria Shalhoub

Moosa Mohammadi

Elena E Pohl

Beate Lanske

Reinhold G Erben

Affiliations

Soon will be listed here.

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.

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