ArticleThe Journal of clinical investigation2016
mTORC2 critically regulates renal potassium handling.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
- Klotho Deficiency Impairs Distal Potassium Homeostasis Through mTORC1-Dependent Suppression of ROMK.Acta physiologica (Oxford, England) · 2026Article
- Renal TRPM6 but not Kv1.1 is required for magnesium homeostasis in mice.American journal of physiology. Renal physiology · 2026Article
- Mechanistic target of rapamycin complex-1 plays a role in inhibiting kidney KAmerican journal of physiology. Renal physiology · 2026Article
- Potassium and the kidney.Nature reviews. Nephrology · 2026Review
- Mechanistic target of rapamycin complex-2 mediates the effect of overnight high KAmerican journal of physiology. Renal physiology · 2026Article
- Pathogenic Role of mTOR Signaling in Cardiometabolic Disease: Implications for Heart, Liver, and Kidney Dysfunction.Physiological research · 2025Review
- Mechanistic Target of Rapamycin Complex 1 in Distal Convoluted Tubule and Renal Potassium Handling.Journal of the American Society of Nephrology : JASN · 2025Article
- Regulation of Glucose Handling in the Kidney: New Layers of Complexity.Journal of the American Society of Nephrology : JASN · 2025Article
- Calcium-Sensing Receptor in the Thick Ascending Limb and Renal Response to Hypercalcemia.Journal of the American Society of Nephrology : JASN · 2025Article
- Impact of aldosterone deficiency on the development of diuretic resistance in mice.Pflugers Archiv : European journal of physiology · 2025Article
- Apolipoprotein-L1 G1 variant contributes to hydrocephalus but not to atherosclerosis in apolipoprotein-E knock-out mice.Clinical science (London, England : 1979) · 2025Article
- Aldosterone-independent regulation of K + secretion in the distal nephron.Current opinion in nephrology and hypertension · 2024Review
- Inhibition of mTORC2 promotes natriuresis in Dahl salt-sensitive rats via the decrease of NCC and ENaC activity.American journal of physiology. Renal physiology · 2024Article
- mTOR Signaling and Human Physiology Relevant to Kidney Disease.Journal of the American Society of Nephrology : JASN · 2024Article
- mTORc2 in Distal Convoluted Tubule and Renal K + Excretion during High Dietary K + Intake.Journal of the American Society of Nephrology : JASN · 2024Article
- Role of calcineurin in regulating renal potassium (KActa physiologica (Oxford, England) · 2024Review
- Low potassium activation of proximal mTOR/AKT signaling is mediated by Kir4.2.Nature communications · 2024Article
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- WNK1 is a chloride-stimulated scaffold that regulates mTORC2 activity and ion transport.Journal of cell science · 2022Article
- Blood pressure effects of sodium transport along the distal nephron.Kidney international · 2022Review
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
The mTOR pathway orchestrates cellular homeostasis. The rapamycin-sensitive mTOR complex (mTORC1) in the kidney has been widely studied; however, mTORC2 function in renal tubules is poorly characterized. Here, we generated mice lacking mTORC2 in the distal tubule (Rictorfl/fl Ksp-Cre mice), which were viable and had no obvious phenotype, except for a 2.5-fold increase in plasma aldosterone. Challenged with a low-Na+ diet, these mice adequately reduced Na+ excretion; however, Rictorfl/fl Ksp-Cre mice rapidly developed hyperkalemia on a high-K+ diet, despite a 10-fold increase in serum aldosterone levels, implying that mTORC2 regulates kaliuresis. Phosphorylation of serum- and glucocorticoid-inducible kinase 1 (SGK1) and PKC-α was absent in Rictorfl/fl Ksp-Cre mice, indicating a functional block in K+ secretion activation via ROMK channels. Indeed, patch-clamp experiments on split-open tubular segments from the transition zone of the late connecting tubule and early cortical collecting duct demonstrated that Ba2+-sensitive apical K+ currents were barely detectable in the majority of Rictorfl/fl Ksp-Cre mice. Conversely, epithelial sodium channel (ENaC) activity was largely preserved, suggesting that the reduced ability to maintain K+ homeostasis is the result of impaired apical K+ conductance and not a reduced electrical driving force for K+ secretion. Thus, these data unravel a vital and nonredundant role of mTORC2 for distal tubular K+ handling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.