Role of ADP-ribosylation factor 6 (ARF6) in gastric acid secretion.
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.
Matsukawa
Jun
J
Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
Nakayama
Kazuhisa
K
Nagao
Taku
T
Ichijo
Hidenori
H
Urushidani
Tetsuro
T
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000737:chemistry* / Q000378:metabolism*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase / Q000737:chemistry; D006632:Histamine / Q000737:chemistry; D006868:Hydrolysis; D007150:Immunohistochemistry; D008274:Magnesium / Q000737:chemistry / Q000494:pharmacology; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D011817:Rabbits; D013347:Subcellular Fractions / Q000378:metabolism
D000089982:ADP-Ribosylation Factor 6; D010455:Peptides; D011500:Protein Synthesis Inhibitors; D020126:Brefeldin A; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006632:Histamine; D017506:H(+)-K(+)-Exchanging ATPase; D020727:ADP-Ribosylation Factors; D008274:Magnesium