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

Am J Physiol Cell Physiol 292: C1485-C1492, 2007. First published December 6, 2006; doi:10.1152/ajpcell.00447.2006
0363-6143/07 $8.00

This Article Free upon publication Full Text Full Text (PDF) All Versions of this Article: 292/4/C1485    most recent 00447.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Hassan, H. A. Articles by Aronson, P. S. Search for Related Content PubMed PubMed Citation Articles by Hassan, H. A. Articles by Aronson, P. S.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Regulation of anion exchanger Slc26a6 by protein kinase C

Departments of ¹Internal Medicine and ²Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut; and ³Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa

Submitted 22 August 2006 ; accepted in final form 27 November 2006

SLC26A6 (CFEX, PAT1) is an anion exchanger expressed in several tissues including renal proximal tubule, pancreatic duct, small intestine, liver, stomach, and heart. It has recently been reported that PKC activation inhibits A6-mediated Cl/HCO₃ exchange by disrupting binding of carbonic anhydrase to A6. However, A6 can operate in HCO₃-independent exchange modes of physiological importance, as A6-mediated Cl/oxalate exchange plays important roles in proximal tubule NaCl reabsorption and intestinal oxalate secretion. We therefore examined whether PKC activation affects HCO₃-independent exchange modes of Slc26a6 functionally expressed in Xenopus oocytes. We found that PKC activation inhibited Cl/formate exchange mediated by Slc26a6 but failed to inhibit the related anion exchanger pendrin (SLC26A4) under identical conditions. PKC activation inhibited Slc26a6-mediated Cl/formate exchange, Cl/oxalate exchange, and Cl/Cl exchange to a similar extent. The inhibitor sensitivity profile and the finding that PMA-induced inhibition was calcium independent suggested a potential role for PKC-. Indeed, the PKC--selective inhibitor rottlerin significantly blocked PMA-induced inhibition of Slc26a6 activity. Localization of Slc26a6 by immunofluorescence microscopy demonstrated that exposure to PKC activation led to redistribution of Slc26a6 from the oocyte plasma membrane to the intracellular compartment immediately below it. We also observed that PMA decreased the pool of Slc26a6 available to surface biotinylation but had no effect on total Slc26a6 expression. The physiological significance of these findings was supported by the observation that PKC activation inhibited mouse duodenal oxalate secretion, an effect blocked by rottlerin. We conclude that multiple modes of anion exchange mediated by Slc26a6 are negatively regulated by PKC- activation.

oxalate; formate; chloride; duodenum

This article has been cited by other articles:

				M. R. Dorwart, N. Shcheynikov, D. Yang, and S. Muallem The Solute Carrier 26 Family of Proteins in Epithelial Ion Transport Physiology, April 1, 2008; 23(2): 104 - 114. [Abstract] [Full Text] [PDF]