mTOR regulates endocytosis and nutrient transport in proximal tubular cells
- Grahammer, Florian Department of Medicine IV, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
- Ramakrishnan, Suresh K. Institute of Anatomy, Department of Medicine, University of Fribourg, Switzerland
- Rinschen, Markus M. Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Germany
- Larionov, Alexey A. Institute of Anatomy, Department of Medicine, University of Fribourg, Switzerland
- Syed, Maryam Institute of Anatomy, Department of Medicine, University of Fribourg, Switzerland
- Khatib, Hazim Department of Medical IV, Sektion Nieren- und Hochdruckkrankheiten, University of Tübingen, Germany
- Roerden, Malte Department of Medical IV, Sektion Nieren- und Hochdruckkrankheiten, University of Tübingen, Germany
- Sass, Jörn Oliver Bioanalytics and Biochemistry, Department of Natural Sciences, Bonn Rhein Sieg University of Applied Sciences, Rheinbach, Germany - Division of Clinical Chemistry and Biochemistry and Children's Research Centre, University Children's Hospital Zürich, Switzerland
- Helmstaedter, Martin Department of Medicine IV, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
- Osenberg, Dorothea Department of Medicine IV, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
- Kühne, Lucas Department of Medicine IV, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
- Kretz, Oliver Department of Medicine IV, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
- Wanner, Nicola Department of Medicine IV, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
- Jouret, Francois Groupe Interdisciplinaire de Génoprotéomique Appliquée, Cardiovascular Sciences, University of Liège, Liege, Belgium
- Benzing, Thomas Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Germany
- Artunc, Ferruh Department of Medical IV, Sektion Nieren- und Hochdruckkrankheiten, University of Tübingen, Germany
- Huber, Tobias B. Department of Medicine IV, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Germany - BIOSS, Centre for Biological Signalling Studies, Center for Biological System Analysis, Albert Ludwigs University of Freiburg, Germany - FRIAS, Freiburg Institute for Advanced Studies and ZBSA, Center for Biological System Analysis, Albert Ludwigs University of Freiburg, Germany
- Theilig, Franziska Institute of Anatomy, Department of Medicine, University of Fribourg, Switzerland
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13.06.2016
Published in:
- Journal of the American Society of Nephrology. - 2017, vol. 28, no. 1, p. 230-241
English
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.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Médecine
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 261153
- DOI 10.1681/ASN.2015111224
- Persistent URL
- https://folia.unifr.ch/unifr/documents/304880
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