Characterization of a novel interaction between the secretory Na +-K+-Cl- cotransporter and the chaperone hsp90

16Citations
Citations of this article
19Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

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-] (Cli-) 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 Cli--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.

Cite

CITATION STYLE

APA

Simard, C. F., Daigle, N. D., Bergeron, M. J., Brunet, G. M., Caron, L., Noël, M., … Isenring, P. (2004). Characterization of a novel interaction between the secretory Na +-K+-Cl- cotransporter and the chaperone hsp90. Journal of Biological Chemistry, 279(46), 48449–48456. https://doi.org/10.1074/jbc.M407012200

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free