ArticleJournal of the American Society of Nephrology : JASN2017
mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells.
Article in Journal of the American Society of Nephrology : JASN, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 104 citations in OpenAlex.
- Effect of everolimus on renal function in patients with tuberous sclerosis complex: evidence from EXIST-1 and EXIST-2.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019Trial
- mTORC1-signaling switches megalin function from endocytosis to cell cycle progression.Cellular and molecular life sciences : CMLS · 2026Article
- mTOR signaling governs the formation of epithelial apical projections via S6K1-RhoA and aPKC-Lgl2 axes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Normalization of trophoblast mTOR signaling rescues impaired function in primary human trophoblast cells isolated from pregnancies complicated by fetal growth restriction.Cell death discovery · 2025Article
- Inactivation mechanisms of NaCommunications biology · 2025Article
- Role of Transport Proteins for the Renal Handling of L-Arginine and Related Derivatives.International journal of molecular sciences · 2025Review
- Regulation of Glucose Handling in the Kidney: New Layers of Complexity.Journal of the American Society of Nephrology : JASN · 2025Article
- Metabolic consequences of altered kidney glucose reabsorption under normoglycemic conditions.Molecular metabolism · 2025Article
- Coordinated Regulation of Renal Glucose Reabsorption and Gluconeogenesis by mTORC2 and Potassium.Journal of the American Society of Nephrology : JASN · 2025Article
- Methylseq, single-nuclei RNAseq, and discovery proteomics identify pathways associated with nephron-deficit CKD in the HSRA rat model.American journal of physiology. Renal physiology · 2025Article
- Protein handling in kidney tubules.Nature reviews. Nephrology · 2025Review
- Megalin: A Sidekick or Nemesis of the Kidney?Journal of the American Society of Nephrology : JASN · 2025Review
- Navigating the Collective: Nanoparticle-Assisted Identification of Leader Cancer Cells During Migration.Life (Basel, Switzerland) · 2025Article
- High glucose couples DJ-1 with PTEN to activate PDGFRβ for renal proximal tubular cell injury.PloS one · 2025Article
- Activation of branched chain amino acid catabolism protects against nephrotoxic acute kidney injury.American journal of physiology. Renal physiology · 2025Article
- Alpha-Synuclein Fails to Form Aggregates in Endocytosis-Defective Fission Yeast Strains, ∆microPublication biology · 2025Article
- Spns1 is an iron transporter essential for megalin-dependent endocytosis.American journal of physiology. Renal physiology · 2024Article
- Low potassium activation of proximal mTOR/AKT signaling is mediated by Kir4.2.Nature communications · 2024Article
- SGLT2-independent effects of canagliflozin on NHE3 and mitochondrial complex I activity inhibit proximal tubule fluid transport and albumin uptake.American journal of physiology. Renal physiology · 2024Article
- Dietary supplementation of cystinotic mice by lysine inhibits the megalin pathway and decreases kidney cystine content.Scientific reports · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
Renal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a conditional mouse genetic approach to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosuria, phosphaturia, aminoaciduria, low molecular weight proteinuria, and albuminuria. Interestingly, proteomics and phosphoproteomics of freshly isolated kidney cortex identified either reduced expression or loss of phosphorylation at critical residues of different classes of specific transport proteins. Functionally, this resulted in reduced nutrient transport and a profound perturbation of the endocytic machinery, despite preserved absolute expression of the main scavenger receptors, MEGALIN and CUBILIN. Our findings highlight a novel mTOR-dependent regulatory network for nutrient transport in renal proximal tubular cells.
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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.