| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 280, Issue 2, 1241-1247, January 14, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
¶
From the
Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521 and the Department of Nephrology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
We investigated the involvement of ClC-3 chloride channels in endosomal acidification by measurement of endosomal pH and chloride concentration [Cl–] in control versus ClC-3-deficient hepatocytes and in control versus ClC-3-transfected Chinese hamster ovary cells. Endosomes were labeled with pH or [Cl–]-sensing fluorescent transferrin (Tf), which targets to early/recycling endosomes, or 
2-macroglobulin (2M), which targets to late endosomes. In pulse label-chase experiments, [Cl–] was 19 mM just after internalization in 2M-labeled endosomes in primary cultures of hepatocytes from wild-type mice, increasing to 58 mM over 45 min, whereas pH decreased from 7.1 to 5.4. Endosomal acidification and [Cl–] accumulation were significantly impaired in hepatocytes from ClC-3 knock-out mice, with [Cl–] increasing from 16 to 43 mM and pH decreasing from 7.1 to 6.0. Acidification and Cl– accumulation were blocked by bafilomycin. In Tf-labeled endosomes, [Cl–] was 46 mM in wild-type versus 35 mM in ClC-3-deficient hepatocytes at 15 min after internalization, with corresponding pH of 6.1 versus 6.5. Approximately 4-fold increased Cl– conductance was found in 2M-labeled endosomes isolated from hepatocytes of wild-type versus ClC-3 null mice. In contrast, Golgi acidification was not impaired in ClC-3-deficient hepatocytes. In transfected Chinese hamster ovary cells expressing ClC-3A, endosomal acidification and [Cl–] accumulation were enhanced. [Cl–] in 2M-labeled endosomes was 42 mM (control) versus 53 mM (ClC-3A) at 45 min, with corresponding pH 5.8 versus 5.2; [Cl–] in Tf-labeled endosomes at 15 min was 37 mM (control) versus 49 mM (ClC-3A) with pH 6.3 versus 5.9. Our results provide direct evidence for involvement of ClC-3 in endosomal acidification by Cl– shunting of the interior-positive membrane potential created by the vacuolar H+ pump.
Received for publication, June 23, 2004 , and in revised form, September 20, 2004.
* This work was supported by National Institutes of Health Grants EB00415, HL73854, HL59198, DK35124, and EY13574 and Grant R613 from the Cystic Fibrosis Foundation. 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: Cardiovascular Research Institute, 1246 Health Sciences East Tower, Box 0521, University of California, San Francisco, CA 94143-0521. Tel.: 415-476-8530; Fax: 415-665-3847; E-mail: verkman{at}itsa.ucsf.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. W. Habela, M. L. Olsen, and H. Sontheimer ClC3 Is a Critical Regulator of the Cell Cycle in Normal and Malignant Glial Cells J. Neurosci., September 10, 2008; 28(37): 9205 - 9217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Okamoto, H. Kajiya, K. Toh, S. Uchida, M. Yoshikawa, S. Sasaki, M. A. Kido, T. Tanaka, and K. Okabe Intracellular ClC-3 chloride channels promote bone resorption in vitro through organelle acidification in mouse osteoclasts Am J Physiol Cell Physiol, March 1, 2008; 294(3): C693 - C701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Reinehr, A. Sommerfeld, V. Keitel, S. Grether-Beck, and D. Haussinger Amplification of CD95 Activation by Caspase 8-induced Endosomal Acidification in Rat Hepatocytes J. Biol. Chem., January 25, 2008; 283(4): 2211 - 2222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Matsuda, M. S. Filali, K. A. Volk, M. M. Collins, J. G. Moreland, and F. S. Lamb Overexpression of CLC-3 in HEK293T cells yields novel currents that are pH dependent Am J Physiol Cell Physiol, January 1, 2008; 294(1): C251 - C262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Haggie and A. S. Verkman Cystic Fibrosis Transmembrane Conductance Regulator-independent Phagosomal Acidification in Macrophages J. Biol. Chem., October 26, 2007; 282(43): 31422 - 31428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhao, X. Li, J. Hao, J. H. Winston, and S. A. Weinman The ClC-3 Chloride Transport Protein Traffics through the Plasma Membrane via Interaction of an N-terminal Dileucine Cluster with Clathrin J. Biol. Chem., September 28, 2007; 282(39): 29022 - 29031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Lassegue How Does the Chloride/Proton Antiporter ClC-3 Control NADPH Oxidase? Circ. Res., September 28, 2007; 101(7): 648 - 650. [Full Text] [PDF]
|
|
|
|
|
|
F. J. Miller Jr, M. Filali, G. J. Huss, B. Stanic, A. Chamseddine, T. J. Barna, and F. S. Lamb Cytokine Activation of Nuclear Factor {kappa}B in Vascular Smooth Muscle Cells Requires Signaling Endosomes Containing Nox1 and ClC-3 Circ. Res., September 28, 2007; 101(7): 663 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Huynh and S. Grinstein Regulation of Vacuolar pH and Its Modulation by Some Microbial Species Microbiol. Mol. Biol. Rev., September 1, 2007; 71(3): 452 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. D. Nascimento, M. A. F. Hayashi, A. Kerkis, V. Oliveira, E. B. Oliveira, G. Radis-Baptista, H. B. Nader, T. Yamane, I. L. dos Santos Tersariol, and I. Kerkis Crotamine Mediates Gene Delivery into Cells through the Binding to Heparan Sulfate Proteoglycans J. Biol. Chem., July 20, 2007; 282(29): 21349 - 21360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H. Weylandt, M. Nebrig, N. Jansen-Rosseck, J. S. Amey, D. Carmena, B. Wiedenmann, C. F. Higgins, and A. Sardini ClC-3 expression enhances etoposide resistance by increasing acidification of the late endocytic compartment Mol. Cancer Ther., March 1, 2007; 6(3): 979 - 986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Jentsch Chloride and the endosomal-lysosomal pathway: emerging roles of CLC chloride transporters J. Physiol., February 1, 2007; 578(3): 633 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Poet, U. Kornak, M. Schweizer, A. A. Zdebik, O. Scheel, S. Hoelter, W. Wurst, A. Schmitt, J. C. Fuhrmann, R. Planells-Cases, et al. Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6 PNAS, September 12, 2006; 103(37): 13854 - 13859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Reinehr, S. Becker, J. Braun, A. Eberle, S. Grether-Beck, and D. Haussinger Endosomal Acidification and Activation of NADPH Oxidase Isoforms Are Upstream Events in Hyperosmolarity-induced Hepatocyte Apoptosis J. Biol. Chem., August 11, 2006; 281(32): 23150 - 23166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Morishita, T. Matsuzaki, M. Hara-chikuma, A. Andoo, M. Shimono, A. Matsuki, K. Kobayashi, M. Ikeda, T. Yamamoto, A. Verkman, et al. Disruption of Aquaporin-11 Produces Polycystic Kidneys following Vacuolization of the Proximal Tubule Mol. Cell. Biol., September 1, 2005; 25(17): 7770 - 7779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lambert and J. Oberwinkler Characterization of a proton-activated, outwardly rectifying anion channel J. Physiol., August 15, 2005; 567(1): 191 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Jentsch Chloride Transport in the Kidney: Lessons from Human Disease and Knockout Mice J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1549 - 1561. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
