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Vol. 14, Issue 3, 1097-1108, March 2003






and
§
Actin cytoskeleton plays an important role in the establishment of
epithelial cell polarity. Cdc42, a member of Rho GTPase family,
modulates actin dynamics via its regulators, such as IQGAP proteins.
Gastric parietal cells are polarized epithelial cells in which
regulated acid secretion occurs in the apical membrane upon
stimulation. We have previously shown that actin isoforms are polarized
to different membrane domains and that the integrity of the actin
cytoskeleton is essential for acid secretion. Herein, we show that
Cdc42 is preferentially distributed to the apical membrane of gastric
parietal cells. In addition, we revealed that two Cdc42 regulators,
IQGAP1 and IQGAP2, are present in gastric parietal cells.
Interestingly, IQGAP2 is polarized to the apical membrane of the
parietal cells, whereas IQGAP1 is mainly distributed to the basolateral
membrane. An IQGAP peptide that competes with full-length IQGAP
proteins for Cdc42-binding in vitro also inhibits acid secretion in
streptolysin-O-permeabilized gastric glands. Furthermore, this peptide
disrupts the association of IQGAP and Cdc42 with the apical actin
cytoskeleton and prevents the apical membrane remodeling upon
stimulation. We propose that IQGAP2 forms a link that associates Cdc42
with the apical cytoskeleton and thus allows for activation of
polarized secretion in gastric parietal cells.
Laboratory of Cell Dynamics, School of Life
Sciences, University of Science and Technology of China, Hefei, China
230027; and
Department of Molecular and Cell
Biology, University of California, Berkeley, California 94720
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