Journal article
On the role of pore helix in regulation of TRPV5 by extracellular protons
The Journal of membrane biology, Vol.212(3), pp.191-198
11/01/2006
DOI: 10.1007/s00232-006-0023-4
PMID: 17334836
Abstract
The transient receptor potential channel TRPV5 is localized to the apical membrane of the distal renal tubule and plays an important role in the regulation of transepithelial Ca2+ reabsorption in kidney. We have previously reported that extracellular protons inhibit TRPV5 by binding to glutamate-522 (E522) in the extracellular domain of the channel. We suggested that E522 is an extracellular "pH sensor" and its titration by extracellular protons inhibits TRPV5 via conformational change(s) of the pore helix. We now report that mutation of a pore helix residue glutamate-535 to glutamine (E535Q) enhances the sensitivity of the channel to inhibition by extracellular protons (i.e., shifting the apparent pKa for inhibition by extracellular protons to the more alkaline extracellular pH). The enhancement of extracellular proton-mediated inhibition of E535Q mutant is also dependent on E522. We have also reported that intracellular acidification enhances the sensitivity of TRPV5 to inhibition by extracellular protons. We now find that modulation of the extracellular proton-mediated inhibition by intracellular acidification is preserved in the E535Q mutant. These results provide further support for the idea that pore helix is involved in the regulation of TRPV5 by extracellular protons. Inhibition of TRPV5 by extracellular protons may contribute to hypercalciuria in diseases associated with high acid load.
Details
- Title: Subtitle
- On the role of pore helix in regulation of TRPV5 by extracellular protons
- Creators
- Byung-Il Yeh - Yonsei UniversityJoonho YoonChou-Long Huang - The University of Texas Southwestern Medical Center
- Resource Type
- Journal article
- Publication Details
- The Journal of membrane biology, Vol.212(3), pp.191-198
- Publisher
- Springer Nature
- DOI
- 10.1007/s00232-006-0023-4
- PMID
- 17334836
- ISSN
- 0022-2631
- eISSN
- 1432-1424
- Number of pages
- 8
- Grant note
- DK-20543 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) P01DK020543 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
- Language
- English
- Date published
- 11/01/2006
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359897502771
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