Regulation of CFTR channel gating.
The debilitating symptoms of cystic fibrosis stem from the reduced Cl- permeability of epithelial cells owing to mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. In cells with normal CFTR channels, receptor-mediated activation of cyclic-AMP-dependent protein kinase causes phosphorylation of several serines in the regulatory domain of CFTR, permitting channel opening and closing via cycles involving ATP hydrolysis. Cellular phosphatases rapidly dephosphorylate the channels, inactivating them. Here we discuss recent advances in our understanding of this complex mechanism for regulating channel gating.
Gadsby
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Laboratory of Cardiac/Membrane Physiology, Rockefeller University, New York, NY 10021.
Nairn
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AC
D000818:Animals; D018118:Chloride Channels / Q000502:physiology*; D003550:Cystic Fibrosis / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006801:Humans; D015640:Ion Channel Gating; D008565:Membrane Proteins / Q000502:physiology*
C505032:CFTR protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator