Physiology and Biochemistry of the Kidney Vacuolar H+-ATPase

Gluck, Stephen L.; Underhill, David; Iyori, Masahiro; Holliday, L. Shannon; Kostrominova, Tatiana Y.; Lee, B S

doi:10.1146/annurev.ph.58.030196.002235

Cited by 111 publications

(100 citation statements)

References 65 publications

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“…1). V-ATPases function in the acidification of a variety of intracellular compartments in eukaryotic cells (2) and in proton secretion from the plasma membrane of some specialized cells in higher organisms (3,4). V-ATPases are required for maintaining the acidity of endosomes, lysosomes, Golgi-derived vesicles, chromaffin granules, the central vacuoles of yeast and plants, and some clathrin-coated vesicles (2).…”

Section: Vacuolar Hmentioning

confidence: 99%

“…V-ATPases are required for maintaining the acidity of endosomes, lysosomes, Golgi-derived vesicles, chromaffin granules, the central vacuoles of yeast and plants, and some clathrin-coated vesicles (2). In some specific cells of the proximal tubule and collecting duct of the kidney, V-ATPases are present at high densities on the plasma membrane and have a central role in maintaining the acid-base balance of the organism (3). In osteoclasts, cells that are essential for bone remodeling, densely packed V-ATPases reside in a specialized domain of the apical plasma membrane known as the ruffled membrane, where they acidify an extracellular compartment at the site of attachment to bone (5).…”

Section: Vacuolar Hmentioning

confidence: 99%

See 1 more Smart Citation

Interaction between Aldolase and Vacuolar H+-ATPase

Lu¹,

Holliday²,

Zhang³

et al. 2001

Journal of Biological Chemistry

174

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Vacuolar H؉ -ATPases (V-ATPases) are essential for acidification of intracellular compartments and for proton secretion from the plasma membrane in kidney epithelial cells and osteoclasts. The cellular proteins that regulate V-ATPases remain largely unknown. A screen for proteins that bind the V-ATPase E subunit using the yeast two-hybrid assay identified the cDNA clone coded for aldolase, an enzyme of the glycolytic pathway. The interaction between E subunit and aldolase was confirmed in vitro by precipitation assays using E subunit-glutathione S-transferase chimeric fusion proteins and metabolically labeled aldolase. Aldolase was isolated associated with intact V-ATPase from bovine kidney microsomes and osteoclast-containing mouse marrow cultures in co-immunoprecipitation studies performed using an anti-E subunit monoclonal antibody. The interaction was not affected by incubation with aldolase substrates or products. In immunocytochemical assays, aldolase was found to colocalize with V-ATPase in the renal proximal tubule. In osteoclasts, the aldolase-V-ATPase complex appeared to undergo a subcellular redistribution from perinuclear compartments to the ruffled membranes following activation of resorption. In yeast cells deficient in aldolase, the peripheral V 1 domain of V-ATPase was found to dissociate from the integral membrane V 0 domain, indicating direct coupling of glycolysis to the proton pump. The direct binding interaction between V-ATPase and aldolase may be a new mechanism for the regulation of the V-ATPase and may underlie the proximal tubule acidification defect in hereditary fructose intolerance. Vacuolar Hϩ -ATPases (V-ATPases) 1 are large multisubunit proteins that are evolutionarily related and structurally similar to the F-ATPases (for a review, see Ref. 1). V-ATPases function in the acidification of a variety of intracellular compartments in eukaryotic cells (2) and in proton secretion from the plasma membrane of some specialized cells in higher organisms (3, 4). V-ATPases are required for maintaining the acidity of endosomes, lysosomes, Golgi-derived vesicles, chromaffin granules, the central vacuoles of yeast and plants, and some clathrin-coated vesicles (2). In some specific cells of the proximal tubule and collecting duct of the kidney, V-ATPases are present at high densities on the plasma membrane and have a central role in maintaining the acid-base balance of the organism (3). In osteoclasts, cells that are essential for bone remodeling, densely packed V-ATPases reside in a specialized domain of the apical plasma membrane known as the ruffled membrane, where they acidify an extracellular compartment at the site of attachment to bone (5). Osteoclast proton secretion is required both for dissolution of bone mineral and for efficient degradation of bone matrix proteins by acid cysteine proteinases (6).During the past decade, much effort has been devoted to isolating genes that encode the subunits of V-ATPases, determining how V-ATPase genes are regulated, and identifying interactions among...

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Section: Vacuolar Hmentioning

confidence: 99%

Section: Vacuolar Hmentioning

confidence: 99%

Interaction between Aldolase and Vacuolar H+-ATPase

Lu¹,

Holliday²,

Zhang³

et al. 2001

Journal of Biological Chemistry

174

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“…One of these genes, AE1, is essential for normal renal bicarbonate reabsorption. The other two genes encode subunits of the vacuolar-type H ϩ ATPase expressed in the apical plasma membrane of type A intercalated cells (ICs) of the collecting duct (CD); this H ϩ pump mediates secretion of protons into tubular fluid and can support a 1,000-fold concentration gradient (7,8). Vacuolar-type H ϩ ATPases are homologous to the ATP synthase of the inner mitochondrial membrane and are composed of at least 13 subunits (9).…”

mentioning

confidence: 99%

The B1-subunit of the H⁺ATPase is required for maximal urinary acidification

Finberg

Wagner

Bailey

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

131

163

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The multisubunit vacuolar-type H ؉ ATPases mediate acidification of various intracellular organelles and in some tissues mediate H ؉ secretion across the plasma membrane. Mutations in the B1-subunit of the apical H ؉ ATPase that secretes protons in the distal nephron cause distal renal tubular acidosis in humans, a condition characterized by metabolic acidosis with an inappropriately alkaline urine. To examine the detailed cellular and organismal physiology resulting from this mutation, we have generated mice deficient in the B1-subunit (Atp6v1b1 ؊/؊ mice). Urine pH is more alkaline and metabolic acidosis is more severe in Atp6v1b1 ؊/؊ mice after oral acid challenge, demonstrating a failure of normal urinary acidification. In Atp6v1b1 ؊/؊ mice, the normal urinary acidification induced by a lumen-negative potential in response to furosemide infusion is abolished. After an acute intracellular acidification, Na ؉ -independent pH recovery rates of individual Atp6v1b1 ؊/؊ intercalated cells of the cortical collecting duct are markedly reduced and show no further decrease after treatment with the selective H ؉ ATPase inhibitor concanamycin. Apical expression of the alternative B-subunit isoform, B2, is increased in Atp6v1b1 ؊/؊ medulla and colocalizes with the H ؉ ATPase E-subunit; however, the greater severity of metabolic acidosis in Atp6v1b1 ؊/؊ mice after oral acid challenge indicates that the B2-subunit cannot fully functionally compensate for the loss of B1. Our results indicate that the B1 isoform is the major B-subunit isoform that incorporates into functional, plasma membrane H ؉ ATPases in intercalated cells of the cortical collecting duct and is required for maximal urinary acidification.collecting duct ͉ intercalated cell ͉ pH homeostasis ͉ renal tubular acidosis ͉ vacuolar H ϩ ATPase

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“…The newly formed CO 2 and H 2 O then diffuse into the PT cells, where carbonic anhydrase II (36,37) catalyzes the regeneration of H ϩ and HCO 3 Ϫ . The cell extrudes the H ϩ across the apical membrane via Na-H exchangers (4,5,30) and H ϩ pumps (20), while exporting the HCO 3 Ϫ across the basolateral membrane, mainly via the electrogenic Na/HCO 3 cotransporter (7,15,32,33).…”

mentioning

confidence: 99%

Effects of angiotensin II on the CO₂dependence of HCO₃⁻reabsorption by the rabbit S2 renal proximal tubule

Zhou¹,

Bouyer²,

Boron³

2006

American Journal of Physiology-Renal Physiology

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M tended to reduce stimulation by CO2, and at 10 Ϫ9 M, produced an even greater reduction. In conclusion, the mutual effects of 1) ANG II on the JHCO 3 response to basolateral CO2 and 2) basolateral CO2 on the JHCO 3 responses to ANG II suggest that the signal-transduction pathways for ANG II and basolateral CO2 intersect or merge.kidney; out-of-equilibrium solutions; acid-base; volume reabsorption ONE OF THE MAJOR tasks of the kidneys is to participate, along with the lungs, in the regulation of the acid-base balance of the extracellular fluid. For example, it has long been appreciated that acute respiratory acidosis (i.e., a rise in PCO 2 that causes a fall in pH) rapidly stimulates renal H ϩ secretion (8, 16). The proximal tubule (PT) plays a key role in this acid secretion. In addition to reabsorbing a near-isosmotic fluid that represents about two-thirds of the fluid filtered by the glomerulus, the PT reabsorbs ϳ80% of the filtered HCO 3 Ϫ as follows. The PT cell actively secretes H ϩ into the tubule lumen (1, 6, 35) and uses this H ϩ to titrate filtered HCO 3 Ϫ in the lumen to CO 2 and H 2 O, catalyzed by apical carbonic anhydrase IV (9, 36, 37). The newly formed CO 2 and H 2 O then diffuse into the PT cells, where carbonic anhydrase II (36, 37) catalyzes the regeneration of H ϩ and HCO 3 Ϫ . The cell extrudes the H ϩ across the apical membrane via Na-H exchangers (4, 5, 30) and H ϩ pumps (20), while exporting the HCO 3 Ϫ across the basolateral membrane, mainly via the electrogenic Na/HCO 3 cotransporter (7,15,32,33 (12) on isolated, perfused rabbit PTs. They noted that adding ϳ2 ϫ 10 Ϫ6 M ANG II to the basolateral solution had no detectable effect on the rate of fluid absorption (J V ). In a 1974 rat micropuncture study, Steven (38) reported that ϳ2 ϫ 10 Ϫ5 M basolateral ANG II lowered J V , whereas 1 ϫ 10 Ϫ7 M had no effect. Harris and Young (23) later showed that basolateral ANG II has a biphasic effect on Na ϩ reabsorption in the rat PT, stimulating at low doses (10 Ϫ12 -10 Ϫ10 M) and inhibiting at higher doses (3 ϫ 10 Ϫ7 -3 ϫ 10 Ϫ6 M). Shuster and colleagues (34) in 1984 demonstrated a similar biphasic effect of basolateral ANG II on J V in isolated, perfused rabbit PTs, ruling out a role of sympathetic innervation on the J V response. In 1991, working in isolated, perfused rat proximal straight tubules (PSTs), Garvin (19) found that 10 Ϫ10 M basolateral ANG II increases both J HCO 3 and J V . At about the same time, Chatsudthipong and Chan (14) found that high levels of basolateral ANG II reduce J HCO 3 in rats and that these effects are blocked by saralasin, an antagonist of ANG II receptors.As far as the effects of luminal ANG II are concerned, in a 1988 micropuncture study, Liu and Cogan (26) showed that low-dose luminal ANG II (10 Ϫ12 -10 Ϫ11 M) increases HCO 3 Ϫ reabsorption (J HCO 3 ) even in a denervated rat kidney. The 1990 study on the rat PT by Wang and Chan (39) extended the earlier observations by showing that increasing levels of luminal ANG II have biphasic effects on J HCO 3 as well...

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Physiology and Biochemistry of the Kidney Vacuolar H+-ATPase

Cited by 111 publications

References 65 publications

Interaction between Aldolase and Vacuolar H+-ATPase

Interaction between Aldolase and Vacuolar H+-ATPase

The B1-subunit of the H⁺ATPase is required for maximal urinary acidification

Effects of angiotensin II on the CO₂dependence of HCO₃⁻reabsorption by the rabbit S2 renal proximal tubule

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Physiology and Biochemistry of the Kidney Vacuolar H+-ATPase

Cited by 111 publications

References 65 publications

Interaction between Aldolase and Vacuolar H+-ATPase

Interaction between Aldolase and Vacuolar H+-ATPase

The B1-subunit of the H+ATPase is required for maximal urinary acidification

Effects of angiotensin II on the CO2dependence of HCO3−reabsorption by the rabbit S2 renal proximal tubule

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The B1-subunit of the H⁺ATPase is required for maximal urinary acidification

Effects of angiotensin II on the CO₂dependence of HCO₃⁻reabsorption by the rabbit S2 renal proximal tubule