|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 16, 13959-13965, April 19, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of The cystic fibrosis transmembrane conductance
regulator (CFTR), which is aberrant in patients with cystic fibrosis,
normally functions both as a chloride channel and as a pleiotropic
regulator of other ion transporters. Here we show, by ratiometric
imaging with luminally exposed pH-sensitive green fluorescent protein, that CFTR affects the pH of cellubrevin-labeled endosomal organelles resulting in hyperacidification of these compartments in cystic fibrosis lung epithelial cells. The excessive acidification of intracellular organelles was corrected with low concentrations of weak
base. Studies with proton ATPase and sodium channel inhibitors showed
that the increased acidification was dependent on proton pump activity
and sodium transport. These observations implicate sodium efflux in the
pH homeostasis of a subset of endocytic organelles and indicate that a
dysfunctional CFTR in cystic fibrosis leads to organellar
hyperacidification in lung epithelial cells because of a loss of CFTR
inhibitory effects on sodium transport. Furthermore, recycling of
transferrin receptor was altered in CFTR mutant cells, suggesting a
previously unrecognized cellular defect in cystic fibrosis, which may
have functional consequences for the receptors on the plasma membrane
or within endosomal compartments.
Hyperacidification of Cellubrevin Endocytic
Compartments and Defective Endosomal Recycling in Cystic Fibrosis
Respiratory Epithelial Cells*
§¶,,
,,§§§
Microbiology and Immunology
and ** Internal Medicine, University of Michigan Medical
School, Ann Arbor, Michigan 48109-0620 and the Departments of
§ Molecular Genetics and Microbiology and
Cell Biology and Physiology, University of
New Mexico, Health Science Center, School of Medicine, Albuquerque,
New Mexico 87131
*
This work was supported by Grant AI31139 from the National
Institutes of Health and Grant 9680 from the Cystic Fibrosis
Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Harvard Medical School, Bldg. D1, Rm. 411, 200 Longwood Ave., Boston, MA 02115.
§§
To whom correspondence should be addressed: Dept. of Molecular
Genetics and Microbiology, Health Science Center, University of New
Mexico, 915 Camino de Salud, N. E., Albuquerque, NM 87131. Tel.:
505-272-0291; Fax: 734-272-5309;
vderetic@salud.unm.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Barriere, M. Bagdany, F. Bossard, T. Okiyoneda, G. Wojewodka, D. Gruenert, D. Radzioch, and G. L. Lukacs Revisiting the Role of Cystic Fibrosis Transmembrane Conductance Regulator and Counterion Permeability in the pH Regulation of Endocytic Organelles Mol. Biol. Cell, July 1, 2009; 20(13): 3125 - 3141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Haggie and A. S. Verkman Defective organellar acidification as a cause of cystic fibrosis lung disease: reexamination of a recurring hypothesis Am J Physiol Lung Cell Mol Physiol, June 1, 2009; 296(6): L859 - L867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Haggie and A. S. Verkman Unimpaired Lysosomal Acidification in Respiratory Epithelial Cells in Cystic Fibrosis J. Biol. Chem., March 20, 2009; 284(12): 7681 - 7686. [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]
|
|
|
|
|
|
J. F. Poschet, G. S. Timmins, J. L. Taylor-Cousar, W. Ornatowski, J. Fazio, E. Perkett, K. R. Wilson, H. D. Yu, H. R. de Jonge, and V. Deretic Pharmacological modulation of cGMP levels by phosphodiesterase 5 inhibitors as a therapeutic strategy for treatment of respiratory pathology in cystic fibrosis Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L712 - L719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Jouret, A. Bernard, C. Hermans, G. Dom, S. Terryn, T. Leal, P. Lebecque, J.-J. Cassiman, B. J. Scholte, H. R. de Jonge, et al. Cystic Fibrosis Is Associated with a Defect in Apical Receptor-Mediated Endocytosis in Mouse and Human Kidney J. Am. Soc. Nephrol., March 1, 2007; 18(3): 707 - 718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. White, D. Jiang, J. D. Burgess, I. R. Bederman, S. F. Previs, and T. J. Kelley Altered cholesterol homeostasis in cultured and in vivo models of cystic fibrosis Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L476 - L486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Delgado, J. F. Poschet, and V. Deretic Nonclassical Pathway of Pseudomonas aeruginosa DNA-Induced Interleukin-8 Secretion in Cystic Fibrosis Airway Epithelial Cells. Infect. Immun., May 1, 2006; 74(5): 2975 - 2984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Swiatecka-Urban, A. Brown, S. Moreau-Marquis, J. Renuka, B. Coutermarsh, R. Barnaby, K. H. Karlson, T. R. Flotte, M. Fukuda, G. M. Langford, et al. The Short Apical Membrane Half-life of Rescued {Delta}F508-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Results from Accelerated Endocytosis of {Delta}F508-CFTR in Polarized Human Airway Epithelial Cells J. Biol. Chem., November 4, 2005; 280(44): 36762 - 36772. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. White, D. A. Corey, and T. J. Kelley Mechanistic Similarities between Cultured Cell Models of Cystic Fibrosis and Niemann-Pick Type C Am. J. Respir. Cell Mol. Biol., November 1, 2004; 31(5): 538 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Swiatecka-Urban, C. Boyd, B. Coutermarsh, K. H. Karlson, R. Barnaby, L. Aschenbrenner, G. M. Langford, T. Hasson, and B. A. Stanton Myosin VI Regulates Endocytosis of the Cystic Fibrosis Transmembrane Conductance Regulator J. Biol. Chem., September 3, 2004; 279(36): 38025 - 38031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Bilan, V. Thoreau, M. Nacfer, R. Derand, C. Norez, A. Cantereau, M. Garcia, F. Becq, and A. Kitzis Syntaxin 8 impairs trafficking of cystic fibrosis transmembrane conductance regulator (CFTR) and inhibits its channel activity J. Cell Sci., April 15, 2004; 117(10): 1923 - 1935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, J. C. Clark, B. J. Aronow, C. R. Dey, C. Liu, J. L. Wooldridge, and J. A. Whitsett Transcriptional Adaptation to Cystic Fibrosis Transmembrane Conductance Regulator Deficiency J. Biol. Chem., February 21, 2003; 278(9): 7674 - 7682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Devuyst and W. B. Guggino Chloride channels in the kidney: lessons learned from knockout animals Am J Physiol Renal Physiol, December 1, 2002; 283(6): F1176 - F1191. [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 |