| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
F508 mutation shortens the biochemical half-life of
plasma membrane CFTR in polarized epithelial cells
1 Research and 3 Medical Services, Veterans Affairs Medical Center and Departments of 2 Medicine and 4 Physiology and Biophysics, The University of Tennessee Health Sciences Center, Memphis, Tennessee 38163
Although the
biosynthetic arrest of the 
F508 mutant of cystic fibrosis
transmembrane conductance regulator (CFTR) can be partially reversed by
physical and chemical means, recent evidence suggests that the
functional stability of the mutant protein after reaching the cell
surface is compromised. To understand the molecular basis for this
observation, the current study directly measured the half-life of
F508 and wild-type CFTR at the cell surface of transfected
LLC-PK1 cells. Plasma membrane CFTR expression over time
was characterized biochemically and functionally in these polarized
epithelial cells. Surface biotinylation, streptavidin extraction, and
quantitative immunoblot analysis determined the biochemical half-life
of plasma membrane F508 CFTR to be ~4 h, whereas the plasma
membrane half-life of wild-type CFTR exceeded 48 h. This
difference in biochemical stability correlated with CFTR-mediated
transport function. These findings indicate that the F508 mutation
decreases the biochemical stability of CFTR at the cell surface. We
conclude that the F508 mutation triggers more rapid internalization
of CFTR and/or its preferential sorting to a pathway of rapid degradation.
cystic fibrosis; regulation; membrane protein; endocytosis; chloride channel; cystic fibrosis transmembrane conductance regulator
This article has been cited by other articles:
|
|
 |
|
  C. Norez, F. Antigny, S. Noel, C. Vandebrouck, and F. Becq A Cystic Fibrosis Respiratory Epithelial Cell Chronically Treated by Miglustat Acquires a Non-Cystic Fibrosis-Like Phenotype Am. J. Respir. Cell Mol. Biol., August 1, 2009; 41(2): 217 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Q. Kang, W. Shen, and R. L. Macdonald Why Does Fever Trigger Febrile Seizures? GABAA Receptor {gamma}2 Subunit Mutations Associated with Idiopathic Generalized Epilepsies Have Temperature-Dependent Trafficking Deficiencies J. Neurosci., March 1, 2006; 26(9): 2590 - 2597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. B. Guggino and S. P. Banks-Schlegel Macromolecular Interactions and Ion Transport in Cystic Fibrosis Am. J. Respir. Crit. Care Med., October 1, 2004; 170(7): 815 - 820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sharma, F. Pampinella, C. Nemes, M. Benharouga, J. So, K. Du, K. G. Bache, B. Papsin, N. Zerangue, H. Stenmark, et al. Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes J. Cell Biol., March 15, 2004; 164(6): 923 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Picciano, N. Ameen, B. D. Grant, and N. A. Bradbury Rme-1 regulates the recycling of the cystic fibrosis transmembrane conductance regulator Am J Physiol Cell Physiol, November 1, 2003; 285(5): C1009 - C1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Bertrand and R. A. Frizzell The role of regulated CFTR trafficking in epithelial secretion Am J Physiol Cell Physiol, July 1, 2003; 285(1): C1 - C18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Loffing-Cueni, J. Loffing, C. Shaw, A. M. Taplin, M. Govindan, C. R. Stanton, and B. A. Stanton Trafficking of GFP-tagged Delta F508-CFTR to the plasma membrane in a polarized epithelial cell line Am J Physiol Cell Physiol, December 1, 2001; 281(6): C1889 - C1897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Weixel and N. A. Bradbury {micro}2 Binding Directs the Cystic Fibrosis Transmembrane Conductance Regulator to the Clathrin-mediated Endocytic Pathway J. Biol. Chem., November 30, 2001; 276(49): 46251 - 46259. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
