|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online September 9, 2005
doi: 10.1242/10.1242/jcs.02525
Research Article |
1 Centro de Estudios Científicos (CECS), Av. Arturo Prat 514, Valdivia, Casilla 1469, Chile
2 Instituto de Histología y Patología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile
3 University of Rochester Medical Center, Rochester, 601 Elmwood Ave., NY 14627, USA
Author for correspondence (e-mail: fsepulveda{at}cecs.cl)
Accepted 7 June 2005
The Cl– channel ClC-2 is expressed in transporting epithelia and has been proposed as an alternative route for Cl– efflux that might compensate for the malfunction of CFTR in cystic fibrosis. There is controversy concerning the cellular and membrane location of ClC-2, particularly in intestinal tissue. The aim of this paper is to resolve this controversy by immunolocalization studies using tissues from ClC-2 knockout animals as control, ascertaining the sorting of ClC-2 in model epithelial cells and exploring the possible molecular signals involved in ClC-2 targeting. ClC-2 was exclusively localized at the basolateral membranes of surface colonic cells or villus duodenal enterocytes. ClC-2 was sorted to the basolateral membranes in MDCK, Caco-2 and LLC-PK1-µ1B, but not in LLC-PK1-µ1A cells. Mutating a di-leucine motif (L812L813) to a di-alanine changed the basolateral targeting of ClC-2 to an apical location. The basolateral membrane localization of ClC-2 in absorptive cells of the duodenum and the colon is compatible with an absorptive function for this Cl– channel. Basolateral targeting information is contained in a di-leucine motif (L812L813) within CBS-2 domain at the C-terminus of ClC-2. It is speculated that ClC-2 also contains an apical sorting signal masked by L812L813. The proposal that CBS domains in ClC channels might behave as regulatory sites sensing intracellular signals opens an opportunity for pharmacological modulation of ClC-2 targeting.
Key words: ClC-2, Intestinal epithelium, Epithelial polarity, MDCK cells, LLC-PK1 cells, CBS domains
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
Related articles in JCS:
This article has been cited by other articles:
|
|
 |
|
  M. I. Niemeyer, L. P. Cid, Y. R. Yusef, R. Briones, and F. V. Sepulveda Voltage-dependent and -independent titration of specific residues accounts for complex gating of a ClC chloride channel by extracellular protons J. Physiol., April 1, 2009; 587(7): 1387 - 1400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nezu, Most. N. Parvin, and R. J. Turner A Conserved Hydrophobic Tetrad near the C Terminus of the Secretory Na+-K+-2Cl- Cotransporter (NKCC1) Is Required for Its Correct Intracellular Processing J. Biol. Chem., March 13, 2009; 284(11): 6869 - 6876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. G. Romanenko, T. Nakamoto, M. A. Catalan, M. Gonzalez-Begne, G. J. Schwartz, Y. Jaramillo, F. V. Sepulveda, C. D. Figueroa, and J. E. Melvin Clcn2 encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands Am J Physiol Gastrointest Liver Physiol, November 1, 2008; 295(5): G1058 - G1067. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. MacDonald, K. R. McKenzie, M. J. Henderson, C. E. Hawkins, N. Vij, and P. L. Zeitlin Lubiprostone activates non-CFTR-dependent respiratory epithelial chloride secretion in cystic fibrosis mice Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L933 - L940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Sorensen, J. E. Matos, M. Sausbier, U. Sausbier, P. Ruth, H. A. Praetorius, and J. Leipziger Aldosterone increases KCa1.1 (BK) channel-mediated colonic K+ secretion J. Physiol., September 1, 2008; 586(17): 4251 - 4264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Heitzmann and R. Warth Physiology and Pathophysiology of Potassium Channels in Gastrointestinal Epithelia Physiol Rev, July 1, 2008; 88(3): 1119 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Bothe, J. Braun, L. Mundhenk, and A. D. Gruber Murine mCLCA6 Is an Integral Apical Membrane Protein of Non-goblet Cell Enterocytes and Co-localizes With the Cystic Fibrosis Transmembrane Conductance Regulator J. Histochem. Cytochem., May 1, 2008; 56(5): 495 - 509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Dohan, C. Portulano, C. Basquin, A. Reyna-Neyra, L. M. Amzel, and N. Carrasco The Na+/I symporter (NIS) mediates electroneutral active transport of the environmental pollutant perchlorate PNAS, December 18, 2007; 104(51): 20250 - 20255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Heitzmann and R. Warth No Potassium, No Acid: K+ Channels and Gastric Acid Secretion Physiology, October 1, 2007; 22(5): 335 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. A. Itani, F. S. Lamb, J. E. Melvin, and M. J. Welsh Basolateral chloride current in human airway epithelia Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L991 - L999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Flores, J. E. Melvin, C. D. Figueroa, and F. V. Sepulveda Abolition of Ca2+-mediated intestinal anion secretion and increased stool dehydration in mice lacking the intermediate conductance Ca2+-dependent K+ channel Kcnn4 J. Physiol., September 1, 2007; 583(2): 705 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Moeser, P. K. Nighot, K. J. Engelke, R. Ueno, and A. T. Blikslager Recovery of mucosal barrier function in ischemic porcine ileum and colon is stimulated by a novel agonist of the ClC-2 chloride channel, lubiprostone Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G647 - G656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hinzpeter, J. Fritsch, F. Borot, S. Trudel, D.-L. Vieu, F. Brouillard, M. Baudouin-Legros, J. Clain, A. Edelman, and M. Ollero Membrane Cholesterol Content Modulates ClC-2 Gating and Sensitivity to Oxidative Stress J. Biol. Chem., January 26, 2007; 282(4): 2423 - 2432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. P. Cid, M. I. Niemeyer, and F. V. Sepulveda ClC-2 channels get new partners. Focus on "Association between Hsp90 and the ClC-2 chloride channel upregulates channel function" Am J Physiol Cell Physiol, January 1, 2006; 290(1): C42 - C44. [Full Text] [PDF]
|
|
