HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 46, 48449-48456, November 12, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/46/48449    most recent M407012200v3 M407012200v2 M407012200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Simard, C. F. Articles by Isenring, P. Search for Related Content PubMed PubMed Citation Articles by Simard, C. F. Articles by Isenring, P. Social Bookmarking                      What's this?

Characterization of a Novel Interaction between the Secretory Na⁺-K⁺-Cl^- Cotransporter and the Chaperone hsp90^*

Charles F. Simard, Nikolas D. Daigle, Marc J. Bergeron, Geneviève M. Brunet, Luc Caron, Micheline Noël, Valérie Montminy, and Paul Isenring, A Canadian Institute of Health and Research Clinician Scientist II

From the Nephrology Research Group, Department of Medicine, Faculty of Medicine, Laval University, Québec, Canada G1R 2J6

The first isoform of the Na⁺-K⁺-Cl^- cotransporter (NKCC1) is of central importance for the control of cellular ion concentration and epithelium-mediated salt secretion. Several studies have established that a change in intracellular [Cl^-] (Cl^-_i) represents a key signaling mechanism by which NKCC1-induced Cl^- movement is autoregulated and by which Cl^- entry and exit on opposite sides of polarized cells are coordinated. Although this signaling mechanism is coupled to a pathway that leads to post-translational modification of the carrier, no unifying model currently accounts for the ion dependence of NKCC1 regulation. In this paper, evidence is presented for the first time that hsp90 associates with the cytosolic C terminus of NKCC1, probably when the carrier is predominantly in its unfolded form during early biogenesis. Evidence is also presented that the Cl^-_i-dependent regulatory pathway can be activated by a thermal stress but that it is no longer operational if NKCC1-expressing cells are pretreated with geldanamycin, an antibiotic that inhibits hsp90, albeit nonspecifically. Taken together, our data indicate that binding of hsp90 to NKCC1 may be required for Na⁺-K⁺-Cl^- cotransport to occur at the cell surface and that it could play an important role in ion-dependent signaling mechanisms, insofar as the maneuvers that were used to alter the expression or activity of the chaperone do not exert their main effect by inducing other cellular events such as the unfolded protein response. Further studies will be required to elucidate the functional relevance of this novel interaction.

Received for publication, June 23, 2004 , and in revised form, September 1, 2004.

^* This work was supported by grants from the Canadian Institute of Health and Research (MT-15405) and the Kidney Foundation of Canada. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: L'Hôtel-Dieu de Québec Research Center, 10 Rue McMahon (Rm. 3852), Québec, Canada G1R 2J6. Tel.: 418-691-5151 (15477); Fax: 418-691-5787; E-mail: paul.isenring{at}crhdq.ulaval.ca.

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

This article has been cited by other articles:

				E. V. Wertheimer, A. M. Salicioni, W. Liu, C. L. Trevino, J. Chavez, E. O. Hernandez-Gonzalez, A. Darszon, and P. E. Visconti Chloride Is Essential for Capacitation and for the Capacitation-associated Increase in Tyrosine Phosphorylation J. Biol. Chem., December 19, 2008; 283(51): 35539 - 35550. [Abstract] [Full Text] [PDF]

				B. Benziane, S. Demaretz, N. Defontaine, N. Zaarour, L. Cheval, S. Bourgeois, C. Klein, M. Froissart, A. Blanchard, M. Paillard, et al. NKCC2 Surface Expression in Mammalian Cells: DOWN-REGULATION BY NOVEL INTERACTION WITH ALDOLASE B J. Biol. Chem., November 16, 2007; 282(46): 33817 - 33830. [Abstract] [Full Text] [PDF]

				A. Hinzpeter, J. Lipecka, F. Brouillard, M. Baudoin-Legros, M. Dadlez, A. Edelman, and J. Fritsch Association between Hsp90 and the ClC-2 chloride channel upregulates channel function Am J Physiol Cell Physiol, January 1, 2006; 290(1): C45 - C56. [Abstract] [Full Text] [PDF]

				I. C. Del Castillo, M. Fedor-Chaiken, J. C. Song, V. Starlinger, J. Yoo, K. S. Matlin, and J. B. Matthews Dynamic regulation of Na+-K+-2Cl- cotransporter surface expression by PKC-{epsilon} in Cl--secretory epithelia Am J Physiol Cell Physiol, November 1, 2005; 289(5): C1332 - C1343. [Abstract] [Full Text] [PDF]

				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]