The Journal of General Physiology
Axon Instruments microelectrode amplifiers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 12 September 2005 doi:10.1085/jgp.200509334
The Rockefeller University Press, 0022-1295 $8.00
JGP, Volume 126, Number 4, 325-337
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2034K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JGP
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brunet, G. M.
Right arrow Articles by Isenring, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brunet, G. M.
Right arrow Articles by Isenring, P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Novel Insights Regarding the Operational Characteristics and Teleological Purpose of the Renal Na+-K+-Cl2 Cotransporter (NKCC2s) Splice Variants

Geneviève M. Brunet, Edith Gagnon, Charles F. Simard, Nikolas D. Daigle, Luc Caron, Micheline Noël, Marie-Hélène Lefoll, Marc J. Bergeron, and Paul Isenring

Nephrology Group, L'Hôtel-Dieu de Québec Research Center, Department of Medicine, Faculty of Medicine, Laval University, Québec, Canada G1R2J6

Correspondence to Paul Isenring: paul.isenring{at}crhdq.ulaval.ca

The absorptive Na+-K+-Cl– cotransporter (NKCC2) is a polytopic protein that forms homooligomeric complexes in the apical membrane of the thick ascending loop of Henle (TAL). It occurs in at least four splice variants (called B, A, F, and AF) that are identical to one another except for a short region in the membrane-associated domain. Although each of these variants exhibits unique functional properties and distributions along the TAL, their teleological purpose and structural organization remain poorly defined. In the current work, we provide additional insight in these regards by showing in mouse that the administration of either furosemide or an H2O-rich diet, which are predicted to alter NKCC2 expression in the TAL, exerts differential effects on mRNA levels for the variants, increasing those of A (furosemide) but decreasing those of F and AF (furosemide or H2O). Based on a yeast two-hybrid mapping analysis, we also show that the formation of homooligomeric complexes is mediated by two self-interacting domains in the COOH terminus (residues 671 to 816 and 910 to 1098), and that these complexes could probably include more than one type of variant. Taken together, the data reported here suggest that A, F, and AF each play unique roles that are adapted to specific physiological needs, and that the accomplishment of such roles is coordinated through the splicing machinery as well as complex NKCC2–NKCC2 interactions.

Abbreviations used in this paper: CCC, cation-Cl cotransporter; Ct, COOH terminus; ctl, control; EIR, essential interacting region; hu, human; ms, mouse; NKCC2, Na+-K+-Cl– cotransporter; OM, outer medulla; RT-PCR, reverse transcriptase PCR; sa, shark; TAL, thick ascending loop of Henle.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
H. Castrop and J. Schnermann
Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and functional significance
Am J Physiol Renal Physiol, October 1, 2008; 295(4): F859 - F866.
[Abstract] [Full Text] [PDF]

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
C. F. Simard, M. J. Bergeron, R. Frenette-Cotton, G. A. Carpentier, M.-E. Pelchat, L. Caron, and P. Isenring
Homooligomeric and Heterooligomeric Associations between K+-Cl- Cotransporter Isoforms and between K+-Cl- and Na+-K+-Cl- Cotransporters
J. Biol. Chem., June 22, 2007; 282(25): 18083 - 18093.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. J. Bergeron, E. Gagnon, L. Caron, and P. Isenring
Identification of Key Functional Domains in the C Terminus of the K+-Cl- Cotransporters
J. Biol. Chem., June 9, 2006; 281(23): 15959 - 15969.
[Abstract] [Full Text] [PDF]


  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents