Insulin-stimulated trafficking of ENaC in renal cells requires PI 3-kinase activity.
Yost, Bonnie L. Blazer, Michail A. Esterman, and Chris J. Vlahos.
1Department of Biology, Indiana University-Purdue University at Indianapolis,
Indianapolis 46202; and 2Therapeutic Area Discovery Research and Chemistry
Information Technology and 3Cardiovascular Research, Lilly Research Laboratories, Eli
Lilly and Company, Indianapolis, Indiana 46285
APStracts 10:0071C, 2003.
aENaC-EGFP (enhanced green fluorescent protein-tagged a-subunit of the epithelial Na+
channel) stably transfected clonal lines derived from the A6 parental cell line were used
to study the physical mechanisms of insulin-stimulated Na+ transport. Within 1 min of
insulin stimulation, ENaC migrates from a diffuse cytoplasmic localization to the apical
and lateral membranes. Concurrently, after insulin stimulation, phosphatidylinositol 3-
kinase (PI 3-kinase) is colocalized with ENaC on the lateral but not apical membrane. An
inhibitor of PI 3-kinase, LY-294002, does not inhibit ENaC/PI 3-kinase colocalization
but does alter the intracellular site of the colocalization, preventing the translocation of
ENaC to the lateral and apical membranes. These data show that insulin stimulation
causes the migration of ENaC to the lateral and apical cell membranes and that this
trafficking is dependent on PI 3-kinase activity.
Received 16 August 2002; accepted in final form 18 February 2003
APS Manuscript Number C372-2.
Article publication pending Am J Physiol Cell Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 25 March 2003