| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The ROMK subtypes of inward-rectifier K+ channels mediate potassium secretion and regulate NaCl reabsorption in the kidney. Loss-of-function mutations in this pH-sensitive K+ channel cause Bartter's disease, a familial salt wasting nephropathy. One disease-causing mutation truncates the extreme COOH-terminus and induces a closed gating conformation. Here we identify a region within the deleted domain that plays an important role in pH-dependent gating. The domain contains a structural element that functionally interacts with the pH sensor in the cytoplasmic NH2-terminus to set a physiological range of pH sensitivity. Removal of the domain shifts the pKa towards alkaline pH values, causing channel inactivation under physiological conditions. Suppressor mutations within the pH sensor rescued channel gating and trans addition of the cognate peptide restored pH sensitivity. A specific interdomain interaction was revealed in an in vitro protein-protein binding assay between the NH2- and COOH-terminal cytoplasmic domains expressed as bacterial fusion proteins. These results provide new insights into the molecular mechanisms underlying Kir channel regulation and channel gating defects that are associated with Bartter's disease.
This article has been cited by other articles:
|
|
 |
|
  C. Huang, A. Sindic, C. E. Hill, K. M. Hujer, K. W. Chan, M. Sassen, Z. Wu, Y. Kurachi, S. Nielsen, M. F. Romero, et al. Interaction of the Ca2+-sensing receptor with the inwardly rectifying potassium channels Kir4.1 and Kir4.2 results in inhibition of channel function Am J Physiol Renal Physiol, March 1, 2007; 292(3): F1073 - F1081. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Wang, J. Su, X. Wang, H. Piao, X. Zhang, C. Y. Adams, N. Cui, and C. Jiang Subunit Stoichiometry of the Kir1.1 Channel in Proton-dependent Gating J. Biol. Chem., April 8, 2005; 280(14): 13433 - 13441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Hebert, G. Desir, G. Giebisch, and W. Wang Molecular Diversity and Regulation of Renal Potassium Channels Physiol Rev, January 1, 2005; 85(1): 319 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Stewart, N. Kerr, M. N. Chernova, S. L. Alper, and R. D. Vaughan-Jones Acute pH-dependent Regulation of AE2-mediated Anion Exchange Involves Discrete Local Surfaces of the NH2-terminal Cytoplasmic Domain J. Biol. Chem., December 10, 2004; 279(50): 52664 - 52676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Coady, M.-H. Chang, F. M. Charron, C. Plata, B. Wallendorff, J. F. Sah, S. D. Markowitz, M. F. Romero, and J.-Y. Lapointe The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter J. Physiol., June 15, 2004; 557(3): 719 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ivanina, D. Varon, S. Peleg, I. Rishal, Y. Porozov, C. W. Dessauer, T. Keren-Raifman, and N. Dascal G{alpha}i1 and G{alpha}i3 Differentially Interact with, and Regulate, the G Protein-activated K+ Channel J. Biol. Chem., April 23, 2004; 279(17): 17260 - 17268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Weeks, G. Gushansky, D. R. Scott, and G. Sachs Mechanism of Proton Gating of a Urea Channel J. Biol. Chem., March 12, 2004; 279(11): 9944 - 9950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yoo, T. P. Flagg, O. Olsen, V. Raghuram, J. K. Foskett, and P. A. Welling Assembly and Trafficking of a Multiprotein ROMK (Kir 1.1) Channel Complex by PDZ Interactions J. Biol. Chem., February 20, 2004; 279(8): 6863 - 6873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yoo, B. Y. Kim, C. Campo, L. Nance, A. King, D. Maouyo, and P. A. Welling Cell Surface Expression of the ROMK (Kir 1.1) Channel Is Regulated by the Aldosterone-induced Kinase, SGK-1, and Protein Kinase A J. Biol. Chem., June 13, 2003; 278(25): 23066 - 23075. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
