Abstract

and/or aims): The applicant proposes to continue studies of the cellular mechanisms regulating gastric acid secretion. The are three specific aims in the current proposal.
The first aim i s to analyze the biochemical events in the pathway that couples the stimulus to parietal cell secretion. An attempt will be made to establish the role of protein phosphorylation in this pathway. The function of two phosphoproteins, one 80 kDa and the other 120 kDa will be examined in detail and the identity of other proteins associated with activation of acid secretion will be sought in a permeabilized gastric gland model.
The second aim i s to characterize the pathways for K+ and Cl- flux present in the apical secretory membrane of stimulated parietal cells. The characteristics of K+ and Cl- transport will be assessed in stimulated apical membrane vesicles. K+ and Cl- channel activity will be analyzed by reconstituting membrane proteins into lipid bilayers. The channel or carrier proteins will be purified and identified.
The third aim i s to characterize the recycling of membranes and proteins associated with the HCl secretory cycle. The components and functional activity of membrane domains during the secretory cycle will be identified and the nature of protein sorting during membrane recycling analyzed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK010141-27
Application #
3224671
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1974-09-01
Project End
1996-02-28
Budget Start
1993-04-25
Budget End
1994-02-28
Support Year
27
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of California Berkeley
Department
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704

  Publications

Grabiner, Mark A; Fu, Zhu; Wu, Tara et al. (2014) Pseudomonas aeruginosa quorum-sensing molecule homoserine lactone modulates inflammatory signaling through PERK and eI-F2?. J Immunol 193:1459-67
Schwarzer, Christian; Fu, Zhu; Shuai, Stacey et al. (2014) Pseudomonas aeruginosa homoserine lactone triggers apoptosis and Bak/Bax-independent release of mitochondrial cytochrome C in fibroblasts. Cell Microbiol 16:1094-104
Watson, Charles; Zhu, Lixin; Guan, Shenheng et al. (2013) Reaction of proton pump inhibitors with model peptides results in novel products. J Pharmacol Sci 122:213-22
Schwarzer, Christian; Fu, Zhu; Patanwala, Maria et al. (2012) Pseudomonas aeruginosa biofilm-associated homoserine lactone C12 rapidly activates apoptosis in airway epithelia. Cell Microbiol 14:698-709
Nakada, Stephanie L; Crothers Jr, James M; Machen, Terry E et al. (2012) Apical vacuole formation by gastric parietal cells in primary culture: effect of low extracellular Ca2+. Am J Physiol Cell Physiol 303:C1301-11
He, Wenjun; Liu, Wensheng; Chew, Catherine S et al. (2011) Acid secretion-associated translocation of KCNJ15 in gastric parietal cells. Am J Physiol Gastrointest Liver Physiol 301:G591-600
Zhu, Lixin; Crothers Jr, James; Zhou, Rihong et al. (2010) A possible mechanism for ezrin to establish epithelial cell polarity. Am J Physiol Cell Physiol 299:C431-43
Zhu, Lixin; Hatakeyama, Jason; Zhang, Bing et al. (2009) Novel insights of the gastric gland organization revealed by chief cell specific expression of moesin. Am J Physiol Gastrointest Liver Physiol 296:G185-95
Zhu, Lixin; Hatakeyama, Jason; Chen, Cheng et al. (2008) Comparative study of ezrin phosphorylation among different tissues: more is good;too much is bad. Am J Physiol Cell Physiol 295:C192-202
Thibodeau, A; Kuo, R C; Crothers Jr, J M et al. (1994) Direct measurement of extracellular proton flux from isolated gastric glands. Am J Physiol 267:C1473-82

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