ArticleAmerican journal of physiology. Renal physiology2013
AMP-activated protein kinase regulates the vacuolar H+-ATPase via direct phosphorylation of the A subunit (ATP6V1A) in the kidney.
Article in American journal of physiology. Renal physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 55 citations in OpenAlex.
- V-ATPase and Lysosomal Energy Sensing in Periodontitis and Medicine-Related Osteonecrosis of the Jaw.Biomolecules · 2025Review
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- The Emerging Roles of Vacuolar-Type ATPase-Dependent Lysosomal Acidification in Cardiovascular Disease.Biomolecules · 2025Review
- Intercalated cell function, kidney innate immunity, and urinary tract infections.Pflugers Archiv : European journal of physiology · 2024Review
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- 14-weeks combined exercise epigenetically modulated 118 genes of menopausal women with prediabetes.Frontiers in endocrinology · 2022Article
- Synaptic tau: A pathological or physiological phenomenon?Acta neuropathologica communications · 2021Review
- The V-ATPaseInternational journal of molecular sciences · 2021Review
- The HAmerican journal of physiology. Cell physiology · 2021Review
- Regulation and function of V-ATPases in physiology and disease.Biochimica et biophysica acta. Biomembranes · 2020Review
- Intercalated Cells of the Kidney Collecting Duct in Kidney Physiology.Seminars in nephrology · 2019Review
- Reciprocal Regulation of V-ATPase and Glycolytic Pathway Elements in Health and Disease.Frontiers in physiology · 2019Review
- AMP-Activated Protein Kinase (AMPK)-Dependent Regulation of Renal Transport.International journal of molecular sciences · 2018Review
- βThe Journal of biological chemistry · 2018Article
- Glucose starvation increases V-ATPase assembly and activity in mammalian cells through AMP kinase and phosphatidylinositide 3-kinase/Akt signaling.The Journal of biological chemistry · 2018Article
- Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane Potential in a Gastric Cancer Cell Line.Scientific reports · 2018Article
- V-ATPases and osteoclasts: ambiguous future of V-ATPases inhibitors in osteoporosis.Theranostics · 2018Review
- The Legionella effector WipB is a translocated Ser/Thr phosphatase that targets the host lysosomal nutrient sensing machinery.Scientific reports · 2017Article
- Activation of the metabolic sensor AMP-activated protein kinase inhibits aquaporin-2 function in kidney principal cells.American journal of physiology. Renal physiology · 2016Article
- Cross-talk between AMP-activated protein kinase and renin-angiotensin system in uninephrectomised rats.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2016Article
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12 authors at 5 institutions in 3 countries.
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Abstract
The vacuolar H(+)-ATPase (V-ATPase) in intercalated cells contributes to luminal acidification in the kidney collecting duct and nonvolatile acid excretion. We previously showed that the A subunit in the cytoplasmic V1 sector of the V-ATPase (ATP6V1A) is phosphorylated by the metabolic sensor AMP-activated protein kinase (AMPK) in vitro and in kidney cells. Here, we demonstrate that treatment of rabbit isolated, perfused collecting ducts with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) inhibited V-ATPase-dependent H(+) secretion from intercalated cells after an acid load. We have identified by mass spectrometry that Ser-384 is a major AMPK phosphorylation site in the V-ATPase A subunit, a result confirmed by comparing AMPK-dependent phosphate labeling of wild-type A-subunit (WT-A) with that of a Ser-384-to-Ala A subunit mutant (S384A-A) in vitro and in intact HEK-293 cells. Compared with WT-A-expressing HEK-293 cells, S384A-A-expressing cells exhibited greater steady-state acidification of HCO3(-)-containing media. Moreover, AICAR treatment of clone C rabbit intercalated cells expressing the WT-A subunit reduced V-ATPase-dependent extracellular acidification, an effect that was blocked in cells expressing the phosphorylation-deficient S384A-A mutant. Finally, expression of the S384A-A mutant prevented cytoplasmic redistribution of the V-ATPase by AICAR in clone C cells. In summary, direct phosphorylation of the A subunit at Ser-384 by AMPK represents a novel regulatory mechanism of the V-ATPase in kidney intercalated cells. Regulation of the V-ATPase by AMPK may couple V-ATPase activity to cellular metabolic status with potential relevance to ischemic injury in the kidney and other tissues.
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