RRC ID 5927
Author Allman E, Johnson D, Nehrke K.
Title Loss of the apical V-ATPase a-subunit VHA-6 prevents acidification of the intestinal lumen during a rhythmic behavior in C. elegans.
Journal 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.
Volume 297(5)
Pages C1071-81
Published 2009-11
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 3.454
Times Cited 23
C.elegans ?