Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV5

Title: Regulation of the epithelial Ca²⁺ channel TRPV5 by reversible histidine phosphorylation mediated by NDPK-B and PHPT1.

Authors: Xinjiang Cai, Shekhar Srivastava, Sheena Surindran, Zhai Li, Edward Y Skolnik

Journal, date & volume: Mol. Biol. Cell, 2014 Apr , 25, 1244-50

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24523290

Abstract
The kidney, together with bone and intestine, plays a crucial role in maintaining whole-body calcium (Ca(2+)) homoeostasis, which is primarily mediated by altering the reabsorption of Ca(2+) filtered by the glomerulus. The transient receptor potential-vanilloid-5 (TRPV5) channel protein forms a six- transmembrane Ca(2+)-permeable channel that regulates urinary Ca(2+) excretion by mediating active Ca(2+) reabsorption in the distal convoluted tubule of the kidney. Here we show that the histidine kinase, nucleoside diphosphate kinase B (NDPK-B), activates TRPV5 channel activity and Ca(2+) flux, and this activation requires histidine 711 in the carboxy-terminal tail of TRPV5. In addition, the histidine phosphatase, protein histidine phosphatase 1, inhibits NDPK-B-activated TRPV5 in inside/out patch experiments. This is physiologically relevant to Ca(2+) reabsorption in vivo, as short hairpin RNA knockdown of NDPK-B leads to decreased TRPV5 channel activity, and urinary Ca(2+) excretion is increased in NDPK-B(-/-) mice fed a high-Ca(2+) diet. Thus these findings identify a novel mechanism by which TRPV5 and Ca(2+) reabsorption is regulated by the kidney and support the idea that histidine phosphorylation plays other, yet-uncovered roles in mammalian biology.