Invited Symposium: Intracellular Traffic of Organelles
Lukacs, G. (Division of Lung Biology, The Hospital for Sick Children, Toronto, Canada)
CFTR predominantly resides at the apical plasma membrane and in the endosomal compartment of epithelia. Constitutive internalization from and recycling back to the cell surface appears to be one of the determinant of CFTR density at the plasma membrane. To explore the mechanism of endocytosis of CFTR, we characterized the internalization pathway and the endosomal sorting signals at the cytoplasmic tails utilizing intact CFTR and chimeric (Tac-CFTR) molecules. Functional analysis of CFTR activity in endosomes and cell surface biotinylation demonstrated that CFTR undergoes clathrin-dependent internalization. Immunofluorescence microscopy and 125I-labeled antibody uptake assay demonstrated that the cytoplasmic tails of CFTR confer highly efficient internalization to the Tac reporter. Inhibition of clathrin-coated vesicle formation also prevented internalization of Tac-CFTR chimeras. Protein phosphorylation by cAMP-dependent protein kinase A and by protein kinase C decreased the internalization rate and contributed to a substantial diminution of the intracellular pool of CFTR. These results suggest that CFTR internalization may participate in the determination and regulation of CFTR chloride channel density and consequently of the cAMP-stimulated chloride conductance of the plasma membrane.
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|Hu, W.; Lukacs, G.; (1998). Cytoplasmic Tails Direct Clathrin-Dependent Endocytosis of CFTR. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/klip/hu0865/index.html|
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