論文 - 詳細
| RRC ID | 5927 |
|---|---|
| 著者 | Allman E, Johnson D, Nehrke K. |
| タイトル | Loss of the apical V-ATPase a-subunit VHA-6 prevents acidification of the intestinal lumen during a rhythmic behavior in C. elegans. |
| ジャーナル | Am J Physiol Cell Physiol |
| Abstract |
In Caenorhabditis elegans, oscillations of intestinal pH contribute to the rhythmic defecation behavior, but the acid-base transport mechanisms that facilitate proton movement are not well understood. Here, we demonstrate that VHA-6, an intestine-specific a-subunit of the H(+)-K(+)-ATPase complex (V-ATPase), resides in the apical membrane of the intestinal epithelial cells and is required for luminal acidification. Disruption of the vha-6 gene led to early developmental arrest; the arrest phenotype could be complemented by expression of a fluorescently labeled vha-6 transgene. To study the contribution of vha-6 to pH homeostasis in larval worms, we used a partial reduction of function through postembryonic single-generation RNA interference. We demonstrate that the inability to fully acidify the intestinal lumen coincides with a defect in pH recovery of the intestinal epithelial cells, suggesting that VHA-6 is essential for proton pumping following defecation. Moreover, intestinal dipeptide accumulation and fat storage are compromised by the loss of VHA-6, suggesting that luminal acidification promotes nutrient uptake in worms, as well as in mammals. Since acidified intracellular vesicles and autofluorescent storage granules are indistinguishable between the vha-6 mutant and controls, it is likely that the nutrient-restricted phenotype is due to a loss of plasma membrane V-ATPase activity specifically. These data establish a simple genetic model for proton pump-driven acidification. Since defecation occurs at 45-s intervals in worms, this model represents an opportunity to study acute regulation of V-ATPase activity on a short time scale and may be useful in the study of alternative treatments for acid-peptic disorders. |
| 巻・号 | 297(5) |
| ページ | C1071-81 |
| 公開日 | 2009-11-1 |
| DOI | 10.1152/ajpcell.00284.2009 |
| PII | 00284.2009 |
| PMID | 19741196 |
| PMC | PMC2777397 |
| MeSH | Animals Behavior, Animal / physiology* Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism* Circadian Rhythm / physiology* Defecation / physiology Gene Expression Regulation, Developmental Hydrogen-Ion Concentration Intestinal Mucosa / metabolism* Microscopy, Confocal Protein Subunits / metabolism RNA Interference Vacuolar Proton-Translocating ATPases / genetics Vacuolar Proton-Translocating ATPases / metabolism* |
| IF | 3.485 |
| 引用数 | 33 |
| WOS 分野 | PHYSIOLOGY CELL BIOLOGY |
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| 各媒体での言及数の合計 | 0 |
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