The role of regulated CFTR trafficking in epithelial secretion.
Bertrand, Carol A., and Raymond A. Frizzell.
Department of Cell Biology and Physiology, University of Pittsburgh School of
Medicine, Pittsburgh, Pennsylvania 15261
APStracts 10:0082C, 2003.
The focus of this review is the regulated trafficking of «cftr» (CFTR) in distal
compartments of the protein secretory pathway and the question of how changes in CFTR
cellular distribution may impact on the functions of polarized epithelial cells. We
summarize data concerning the cellular localization and activity of CFTR and attempt to
synthesize often conflicting results from functional studies of regulated endocytosis and
exocytosis in CFTR-expressing cells. In some instances, findings that are inconsistent
with regulated CFTR trafficking may result from the use of overexpression systems or
nonphysiological experimental conditions. Nevertheless, judging from data on other
transporters, an appropriate cellular context is necessary to support regulated CFTR
trafficking, even in epithelial cells. The discovery that disease mutations can influence
CFTR trafficking in distal secretory and recycling compartments provides support for the
concept that regulated CFTR recycling contributes to normal epithelial function,
including the control of apical CFTR channel density and epithelial protein secretion.
Finally, we propose molecular mechanisms for regulated CFTR endocytosis and
exocytosis that are based on CFTR interactions with other proteins, particularly those
whose primary function is membrane trafficking. These models provide testable
hypotheses that may lead to elucidation of CFTR trafficking mechanisms and permit their
experimental manipulation in polarized epithelial cells.
APS Manuscript Number C554-2.
Article publication pending Am J Physiol Cell Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 25 March 2003