Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV5

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

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

Journal, date & volume: EMBO J., 2014 Feb 3 , 33, 229-46

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24434184

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.