JBC Avanti Polar Lipids

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Originally published In Press as doi:10.1074/jbc.C200021200 on January 28, 2002

J. Biol. Chem., Vol. 277, Issue 11, 8767-8770, March 15, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
277/11/8767    most recent
C200021200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Giménez, I.
Right arrow Articles by Forbush, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Giménez, I.
Right arrow Articles by Forbush, B.

ACCELERATED PUBLICATION
Spatially Distributed Alternative Splice Variants of the Renal Na-K-Cl Cotransporter Exhibit Dramatically Different Affinities for the Transported Ions*

Ignacio GiménezDagger , Paul Isenring§, and Biff Forbush

From the Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06511

Three splice variants of the renal Na-K-Cl cotransporter (NKCC2 F, A, and B) are spatially distributed along the thick ascending limb of the mammalian kidney. To test whether NKCC2 splice variants differ in ion transport characteristics we expressed cDNAs encoding rabbit NKCC2 F, A, and B in Xenopus oocytes and determined the ion dependence of bumetanide-sensitive 86Rb influx. The three splice variants of NKCC2 showed dramatic differences in their kinetic behavior. The medullary variant F exhibited 3-4-fold lower affinity than variants A and B for Na+ and K+. Chloride affinities also markedly distinguish the three variants (KmF = 111.3, KmA = 44.7, and KmB = 8.9 mM Cl-). Thus, the kinetic properties of the NKCC2 splice variants are consistent with the spatial distribution of the variants along the thick ascending limb as they are involved in reabsorbing Na+, K+, and Cl- from a progressively diluted fluid in the tubule lumen. Variant B also showed an anomalous inhibition of rubidium influx at high extracellular Na+ concentrations, possibly important in its highly specialized role in the macula densa. The adaptation of the kinetic characteristics of the NKCC2 variants to the luminal concentrations of substrate represents an excellent example of functional specialization and diversity that can be achieved through alternative mRNA splicing.


* This research was supported by National Institutes of Health Grant DK-17433 and a fellowship (to I. G.) from the Ministerio de Educación y Cultura of Spain.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520-8026. Tel.: 203-7373-2586; Fax: 203-785-6834; E-mail: ignacio.gimenez@yale.edu.

§ Present address: Groupe de Recherche en Nephrologie, Dept. of Medicine, Faculty of Medicine, Laval University, Quebec G1R 2J6, Canada.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


This article has been cited by other articles:


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
S. N. Orlov and A. A. Mongin
Salt-sensing mechanisms in blood pressure regulation and hypertension
Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2039 - H2053.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
I. Gimenez and B. Forbush
The Residues Determining Differences in Ion Affinities among the Alternative Splice Variants F, A, and B of the Mammalian Renal Na-K-Cl Cotransporter (NKCC2)
J. Biol. Chem., March 2, 2007; 282(9): 6540 - 6547.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
M. Oppermann, D. Mizel, S. M. Kim, L. Chen, R. Faulhaber-Walter, Y. Huang, C. Li, C. Deng, J. Briggs, J. Schnermann, et al.
Renal Function in Mice with Targeted Disruption of the A Isoform of the Na-K-2Cl Co-Transporter
J. Am. Soc. Nephrol., February 1, 2007; 18(2): 440 - 448.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
M. Oppermann, D. Mizel, G. Huang, C. Li, C. Deng, F. Theilig, S. Bachmann, J. Briggs, J. Schnermann, and H. Castrop
Macula Densa Control of Renin Secretion and Preglomerular Resistance in Mice with Selective Deletion of the B Isoform of the Na,K,2Cl Co-Transporter
J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2143 - 2152.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
E. Moreno, P. S. Cristobal, M. Rivera, N. Vazquez, N. A. Bobadilla, and G. Gamba
Affinity-defining Domains in the Na-Cl Cotransporter: A DIFFERENT LOCATION FOR Cl- AND THIAZIDE BINDING
J. Biol. Chem., June 23, 2006; 281(25): 17266 - 17275.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
A. Paredes, C. Plata, M. Rivera, E. Moreno, N. Vazquez, R. Munoz-Clares, S. C. Hebert, and G. Gamba
Activity of the renal Na+-K+-2Cl- cotransporter is reduced by mutagenesis of N-glycosylation sites: role for protein surface charge in Cl- transport
Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1094 - F1102.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
D. B. Mount
Membrane trafficking and the regulation of NKCC2
Am J Physiol Renal Physiol, March 1, 2006; 290(3): F606 - F607.
[Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
I. Gimenez and B. Forbush
Regulatory phosphorylation sites in the NH2 terminus of the renal Na-K-Cl cotransporter (NKCC2)
Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1341 - F1345.
[Abstract] [Full Text] [PDF]


Home page
J. Gen. Physiol.Home page
G. M. Brunet, E. Gagnon, C. F. Simard, N. D. Daigle, L. Caron, M. Noel, M.-H. Lefoll, M. J. Bergeron, and P. Isenring
Novel Insights Regarding the Operational Characteristics and Teleological Purpose of the Renal Na+-K+-Cl2 Cotransporter (NKCC2s) Splice Variants
J. Gen. Physiol., September 26, 2005; 126(4): 325 - 337.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
E. Gagnon, M. J. Bergeron, N. D. Daigle, M.-H. Lefoll, and P. Isenring
Molecular Mechanisms of Cation Transport by the Renal Na+-K+-Cl- Cotransporter: STRUCTURAL INSIGHT INTO THE OPERATING CHARACTERISTICS OF THE ION TRANSPORT SITES
J. Biol. Chem., September 16, 2005; 280(37): 32555 - 32563.
[Abstract] [Full Text] [PDF]


Home page
Physiol. Rev.Home page
G. Gamba
Molecular Physiology and Pathophysiology of Electroneutral Cation-Chloride Cotransporters
Physiol Rev, April 1, 2005; 85(2): 423 - 493.
[Abstract] [Full Text] [PDF]


Home page
J. Exp. Biol.Home page
J. P. Ianowski, R. J. Christensen, and M. J. O'Donnell
Na+ competes with K+ in bumetanide-sensitive transport by Malpighian tubules of Rhodnius prolixus
J. Exp. Biol., October 1, 2004; 207(21): 3707 - 3716.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
C. Tovar-Palacio, N. A. Bobadilla, P. Cortes, C. Plata, P. de los Heros, N. Vazquez, and G. Gamba
Ion and diuretic specificity of chimeric proteins between apical Na+-K+-2Cl- and Na+-Cl- cotransporters
Am J Physiol Renal Physiol, September 1, 2004; 287(3): F570 - F577.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
E. Moreno, C. Tovar-Palacio, P. de los Heros, B. Guzman, N. A. Bobadilla, N. Vazquez, D. Riccardi, E. Poch, and G. Gamba
A Single Nucleotide Polymorphism Alters the Activity of the Renal Na+:Cl- Cotransporter and Reveals a Role for Transmembrane Segment 4 in Chloride and Thiazide Affinity
J. Biol. Chem., April 16, 2004; 279(16): 16553 - 16560.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
E. Gagnon, M. J. Bergeron, G. M. Brunet, N. D. Daigle, C. F. Simard, and P. Isenring
Molecular Mechanisms of Cl- Transport by the Renal Na+-K+-Cl- Cotransporter: IDENTIFICATION OF AN INTRACELLULAR LOCUS THAT MAY FORM PART OF A HIGH AFFINITY Cl--BINDING SITE
J. Biol. Chem., February 13, 2004; 279(7): 5648 - 5654.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
P. G.J.F. Starremans, F. F.J. Kersten, L. P.W.J. van den Heuvel, N. V.A.M. Knoers, and R. J.M. Bindels
Dimeric Architecture of the Human Bumetanide-Sensitive Na-K-Cl Co-transporter
J. Am. Soc. Nephrol., December 1, 2003; 14(12): 3039 - 3046.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
I. Gimenez and B. Forbush
Short-term Stimulation of the Renal Na-K-Cl Cotransporter (NKCC2) by Vasopressin Involves Phosphorylation and Membrane Translocation of the Protein
J. Biol. Chem., July 11, 2003; 278(29): 26946 - 26951.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
M. J. Bergeron, E. Gagnon, B. Wallendorff, J.-Y. Lapointe, and P. Isenring
Ammonium transport and pH regulation by K+-Cl- cotransporters
Am J Physiol Renal Physiol, July 1, 2003; 285(1): F68 - F78.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
P. G.J.F. Starremans, F. F.J. Kersten, N. V.A.M. Knoers, L. P.W.J. van den Heuvel, and R. J.M. Bindels
Mutations in the Human Na-K-2Cl Cotransporter (NKCC2) Identified in Bartter Syndrome Type I Consistently Result in Nonfunctional Transporters
J. Am. Soc. Nephrol., June 1, 2003; 14(6): 1419 - 1426.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
J. Schnermann
The Juxtaglomerular Apparatus: From Anatomical Peculiarity to Physiological Relevance
J. Am. Soc. Nephrol., June 1, 2003; 14(6): 1681 - 1694.
[Full Text] [PDF]


Home page
Am. J. Physiol. Cell Physiol.Home page
E. Gagnon, B. Forbush, L. Caron, and P. Isenring
Functional comparison of renal Na-K-Cl cotransporters between distant species
Am J Physiol Cell Physiol, February 1, 2003; 284(2): C365 - C370.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
S. S. Shankar and D. C. Brater
Loop diuretics: from the Na-K-2Cl transporter to clinical use
Am J Physiol Renal Physiol, January 1, 2003; 284(1): F11 - F21.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
E. Gagnon, B. Forbush, A. W. Flemmer, I. Gimenez, L. Caron, and P. Isenring
Functional and molecular characterization of the shark renal Na-K-Cl cotransporter: novel aspects
Am J Physiol Renal Physiol, November 1, 2002; 283(5): F1046 - F1055.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
J. N. Lorenz, N. R. Baird, L. M. Judd, W. T. Noonan, A. Andringa, T. Doetschman, P. A. Manning, L. H. Liu, M. L. Miller, and G. E. Shull
Impaired Renal NaCl Absorption in Mice Lacking the ROMK Potassium Channel, a Model for Type II Bartter's Syndrome
J. Biol. Chem., September 27, 2002; 277(40): 37871 - 37880.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.