Role of ADP-ribosylation factor 6 (ARF6) in gastric acid secretion
Role of ADP-ribosylation factor 6 (ARF6) in gastric acid secretion
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DOI：
10.1074/jbc.m305444200
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发表时间：
2003-09-19
影响因子：
4.8
通讯作者：
Urushidani, T
中科院分区：
文献类型：
--
作者：
Matsukawa, J;Nakayama, K;Urushidani, T
ADP-核糖化因子(ARF)蛋白是一类单体GTP酶，在许多分泌细胞的膜转运和胞吐过程中起重要作用。我们研究了ARF6，它的激活对灯盏花素A不敏感，以确定它是否调节胃壁细胞的膜运输。在GTPGammaS的存在下，ARF6从胞浆转位到小管泡膜，而在镁离子螯合的条件下，ARF-GTPase激活蛋白的活性被抑制，ARF6转位到顶端分泌膜。免疫组织化学显示ARF6主要定位于胃腺内的壁细胞，刺激胃腺后ARF6由胞浆移位至细胞内小管。这些结果表明，ARF6在细胞质和两种不同膜之间的分配受其GTP酶活性的调节。在培养的胃腺中，表达ARF6 Q67L的腺病毒感染后，胃酸分泌受到抑制。这些结果表明，ARF6调节壁细胞胃酸分泌，ARF6的GTP水解循环是激活途径所必需的。
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.