Polarized gp2 secretion in mdck cells via gpi targeting and apical
membrane restricted proteolysis.
Fritz, Benjamin A., Anson W. Lowe.
The Department of Medicine and the Digestive Disease Center,
Stanford University, Stanford, California 94305-5487
APStracts 2:0157G, 1995.
The major zymogen granule membrane protein in the exocrine pancreas is
GP2, a glycosyl-phosphatidylinositol (GPI) linked membrane protein.
Despite its GPI anchor, GP2 is secreted into the pancreatic duct. We
examined the mechanism underlying the secretion of GP2 in isolated
pancreatic acini and transfected MDCK cells (MDCK-GP2). MDCK-GP2
cells release GP2 almost exclusively (>95%) from the apical
membrane. Using GP2 as a model, we defined a novel mechanism of
polarized protein secretion in which a secretory protein is targeted
via a GPI anchor to the apical plasma membrane, whereupon the mature
form is released by proteolysis. Furthermore, we described two
features of MDCK cells which enhance the polarized release of GP2: an
apical plasma membrane-restricted distribution of the protease
responsible for GP2 membrane cleavage, and a transcytotic pathway to
re-route basolateral plasma membrane GP2 to the apical cell surface.
Received 13 April 1995; accepted in final form 27 July 1995.
APS Manuscript Number G155-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.