| First Author | Andrukhova O | Year | 2014 |
| Journal | EMBO J | Volume | 33 |
| Issue | 3 | Pages | 229-46 |
| PubMed ID | 24434184 | Mgi Jnum | J:206448 |
| Mgi Id | MGI:5550300 | Doi | 10.1002/embj.201284188 |
| Citation | Andrukhova O, et al. (2014) FGF23 promotes renal calcium reabsorption through the TRPV5 channel. EMBO J 33(3):229-46 |
| abstractText | alphaKlotho 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, alphaKlotho 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 alphaKlotho knockout mice. We further demonstrate that alphaKlotho 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-alphaKlotho complex and activates a signaling cascade involving ERK1/2, SGK1, and WNK4. Our data thereby identify FGF23, not alphaKlotho, as a calcium-conserving hormone in the kidney. |
