Overexpression of r domain eliminates camp stimulated chloride
secretion in 9/hteo-cells in culture.
Perez, Aura, Kimberly A. Risma, Elizabeth A. Eckman, and Pamela B.
Davis.
Departments of Pediatrics, and Molecular Biology and Microbiology,
Case Western Reserve University at Rainbow Babies and Childrens
Hospital, Cleveland, OH 44106
APStracts 3:0031L, 1996.
The intracellular hydrophilic region of the cystic fibrosis
transmembrane conductance regulator (CFTR), the R domain, has been
postulated to be a regulator of the Cl- channel: under basal
conditions R blocks the channel, but when phosphorylated, R undergoes
conformational change to open the channel. Overexpression of R in
9/HTEo- cells, a human tracheal epithelial cell line with cAMP
-regulated Cl- conductance due to CFTR, caused reduced basal Cl-
conductance and elimination of its response to isoproterenol, but
ionomycin-stimulated Cl- efflux was preserved. Cells which
overexpressed R showed no downregulation of endogenous CFTR mRNA, and
had normal cAMP production and PKA activity, so R did not act at
these levels. Although the precise mechanism by which R affects CFTR
conductance is undetermined, these cell lines could be useful in
separating the cell biologic consequences of impaired Cl- transport
from those of mutant CFTR, per se.
Received 21 June 1994; accepted in final form 12 February 1996.
APS Manuscript Number L183-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96