Article (Scientific journals)
mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells.
Grahammer, Florian; Ramakrishnan, Suresh K.; Rinschen, Markus M. et al.
2016In Journal of the American Society of Nephrology
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Keywords :
albuminuria; endocytosis; epithelial transport; mTOR; proteomics; proximal tubule
Abstract :
[en] 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.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
Grahammer, Florian
Ramakrishnan, Suresh K.
Rinschen, Markus M.
Larionov, Alexey A.
Syed, Maryam
Khatib, Hazim
Roerden, Malte
Sass, Jorn Oliver
Helmstaedter, Martin
Osenberg, Dorothea
Kuhne, Lucas
Kretz, Oliver
Wanner, Nicola
Jouret, François  ;  Université de Liège > Département des sciences cliniques > Néphrologie
Benzing, Thomas
Artunc, Ferruh
Huber, Tobias B.
Theilig, Franziska
More authors (8 more) Less
Language :
English
Title :
mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells.
Publication date :
2016
Journal title :
Journal of the American Society of Nephrology
ISSN :
1046-6673
eISSN :
1533-3450
Publisher :
Lippincott Williams and Wilkins, Washington, United States - District of Columbia
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2016 by the American Society of Nephrology.
Available on ORBi :
since 05 September 2016

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