title: Polarized distribution of IQGAP proteins in gastric parietal cells and their roles in regulated epithelial cell secretion.
abstract: 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.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
authors.forename: Rihong
authors.initials: R
authors.lastname: Zhou
authors.forename: Zhen
authors.initials: Z
authors.lastname: Guo
authors.forename: Charles
authors.initials: C
authors.lastname: Watson
authors.forename: Emily
authors.initials: E
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Kong
authors.forename: Wenxian
authors.initials: W
authors.lastname: Wang
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins; D000099149:Ezrin
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D010455:Peptides; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D020764:cdc42 GTP-Binding Protein; D020703:ras GTPase-Activating Proteins; D000099149:Ezrin; C101203:IQ motif containing GTPase activating protein 1; C101002:IQGAP2 protein, human