Vesicular targeting and the control of ion secretion in epithelial cells: implications for cystic fibrosis.
Non-polarized HT-29 colonic epithelial cells fail to respond to cyclic AMP-generating agonists with increases in plasma membrane anion conduction. Radio-isotopic efflux and patch-clamp experiments revealed that both undifferentiated and differentiated HT-29 colonocytes possess volume- and Ca(2+)-activated Cl- channels. However, only within the apical plasma membranes of the latter were cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels found. CFTR was expressed equally well in both non-polarized and polarized colonocytes. Lack of CFTR-dependent anion conduction was shown to be the result of CFTR retention within a peripheral intracellular compartment. We demonstrate that upon polarization, CFTR moves to the apical plasma membrane via a Brefeldin A (BFA)-sensitive intracellular trafficking pathway.
Cunningham
S A
SA
Texas Biotechnology Corporation, Houston 77030, USA.
Frizzell
R A
RA
Morris
A P
AP
D000818:Animals; D003550:Cystic Fibrosis / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism*; D006801:Humans; D007477:Ions
D007477:Ions