1. Role of ADP-ribosylation factor 6 (ARF6) in gastric acid secretion.
- Author
-
Matsukawa J, Nakayama K, Nagao T, Ichijo H, and Urushidani T
- Subjects
- ADP-Ribosylation Factor 6, Adenoviridae genetics, Animals, Brefeldin A pharmacology, Cell Membrane metabolism, Cytosol metabolism, Gastric Mucosa metabolism, Guanosine 5'-O-(3-Thiotriphosphate) metabolism, H(+)-K(+)-Exchanging ATPase chemistry, Histamine chemistry, Hydrolysis, Immunohistochemistry, Magnesium chemistry, Magnesium pharmacology, Mutation, Peptides chemistry, Protein Synthesis Inhibitors pharmacology, Protein Transport, Rabbits, Subcellular Fractions metabolism, ADP-Ribosylation Factors chemistry, ADP-Ribosylation Factors metabolism, Gastric Acid metabolism
- Abstract
ADP-ribosylation factor (ARF) proteins are monomeric GTPases that are essential for membrane transport and exocytosis in a number of secretory cells. We investigated ARF6, the activation of which is insensitive to brefeldin A, to determine whether it regulates membrane traffic in gastric parietal cells. ARF6 translocated from cytosol to tubulovesicle in the presence of GTPgammaS, a potential inhibitor of acid secretion in permeabilized cells, whereas under the Mg2+-chelated condition where activity of ARF-GTPase activating protein is inhibited, ARF6 translocated to the apical secretory membrane. Immunohistochemical examination revealed that ARF6 mainly located in parietal cell within the gastric glands, and it translocated from the cytosol to the intracellular canaliculi when the glands were stimulated. These results indicated that the distribution of ARF6 between cytosol and the two different membranes was regulated by its GTPase activity. In cultured gastric glands infected with adenovirus expressing ARF6 Q67L, a mutant lacking GTP hydrolysis activity, gastric acid secretion was inhibited. These results suggest that ARF6 regulates gastric acid secretion in parietal cell and that the GTP hydrolysis cycle of ARF6 is essential for the activation pathway.
- Published
- 2003
- Full Text
- View/download PDF