Myosin VI Regulates Endocytosis of the Cystic Fibrosis Transmembrane Conductance Regulator

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-regulated Cl- channel expressed in the apical plasma membrane in fluid-transporting epithelia. Although CFTR is rapidly endocytosed from the apical membrane of polarized epithelial cells and efficiently recycled back to t...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-09, Vol.279 (36), p.38025-38031
Main Authors: Swiatecka-Urban, Agnieszka, Boyd, Cary, Coutermarsh, Bonita, Karlson, Katherine H., Barnaby, Roxanna, Aschenbrenner, Laura, Langford, George M., Hasson, Tama, Stanton, Bruce A.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Adaptor Proteins, Vesicular Transport - metabolism
Apoptosis Regulatory Proteins
Base Sequence
Cell Line
Clathrin - metabolism
Cystic Fibrosis Transmembrane Conductance Regulator - physiology
DNA Primers
Endocytosis - physiology
Genes, Tumor Suppressor
Humans
Myosin Heavy Chains - physiology
Protein Binding
Reverse Transcriptase Polymerase Chain Reaction
Trachea - cytology
Trachea - metabolism
Tumor Suppressor Proteins
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Summary:The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-regulated Cl- channel expressed in the apical plasma membrane in fluid-transporting epithelia. Although CFTR is rapidly endocytosed from the apical membrane of polarized epithelial cells and efficiently recycled back to the plasma membrane, little is known about the molecular mechanisms regulating CFTR endocytosis and endocytic recycling. Myosin VI, an actin-dependent, minus-end directed mechanoenzyme, has been implicated in clathrin-mediated endocytosis in epithelial cells. The goal of this study was to determine whether myosin VI regulates CFTR endocytosis. Endogenous, apical membrane CFTR in polarized human airway epithelial cells (Calu-3) formed a complex with myosin VI, the myosin VI adaptor protein Disabled 2 (Dab2), and clathrin. The tail domain of myosin VI, a dominant-negative recombinant fragment, displaced endogenous myosin VI from interacting with Dab2 and CFTR and increased the expression of CFTR in the plasma membrane by reducing CFTR endocytosis. However, the myosin VI tail fragment had no effect on the recycling of endocytosed CFTR or on fluid-phase endocytosis. CFTR endocytosis was decreased by cytochalasin D, an actin-filament depolymerizing agent. Taken together, these data indicate that myosin VI and Dab2 facilitate CFTR endocytosis by a mechanism that requires actin filaments.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M403141200