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mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells

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mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells. / Grahammer, Florian; Ramakrishnan, Suresh K; Rinschen, Markus M; Larionov, Alexey A; Syed, Maryam; Khatib, Hazim; Roerden, Malte; Sass, Jörn Oliver; Helmstaedter, Martin; Osenberg, Dorothea; Kühne, Lucas; Kretz, Oliver; Wanner, Nicola; Jouret, Francois; Benzing, Thomas; Artunc, Ferruh; Huber, Tobias B; Theilig, Franziska.

In: J AM SOC NEPHROL, Vol. 28, No. 1, 01.2017, p. 230-241.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Grahammer, F, Ramakrishnan, SK, Rinschen, MM, Larionov, AA, Syed, M, Khatib, H, Roerden, M, Sass, JO, Helmstaedter, M, Osenberg, D, Kühne, L, Kretz, O, Wanner, N, Jouret, F, Benzing, T, Artunc, F, Huber, TB & Theilig, F 2017, 'mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells', J AM SOC NEPHROL, vol. 28, no. 1, pp. 230-241. https://doi.org/10.1681/ASN.2015111224

APA

Grahammer, F., Ramakrishnan, S. K., Rinschen, M. M., Larionov, A. A., Syed, M., Khatib, H., Roerden, M., Sass, J. O., Helmstaedter, M., Osenberg, D., Kühne, L., Kretz, O., Wanner, N., Jouret, F., Benzing, T., Artunc, F., Huber, T. B., & Theilig, F. (2017). mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells. J AM SOC NEPHROL, 28(1), 230-241. https://doi.org/10.1681/ASN.2015111224

Vancouver

Grahammer F, Ramakrishnan SK, Rinschen MM, Larionov AA, Syed M, Khatib H et al. mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells. J AM SOC NEPHROL. 2017 Jan;28(1):230-241. https://doi.org/10.1681/ASN.2015111224

Bibtex

@article{0e5ea19590554138a6fa6f1bdfbb30f1,
title = "mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells",
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.",
keywords = "Animals, Endocytosis, Kidney Tubules, Proximal, Mice, Multiprotein Complexes, Protein Transport, TOR Serine-Threonine Kinases, Journal Article",
author = "Florian Grahammer and Ramakrishnan, {Suresh K} and Rinschen, {Markus M} and Larionov, {Alexey A} and Maryam Syed and Hazim Khatib and Malte Roerden and Sass, {J{\"o}rn Oliver} and Martin Helmstaedter and Dorothea Osenberg and Lucas K{\"u}hne and Oliver Kretz and Nicola Wanner and Francois Jouret and Thomas Benzing and Ferruh Artunc and Huber, {Tobias B} and Franziska Theilig",
note = "Copyright {\textcopyright} 2016 by the American Society of Nephrology.",
year = "2017",
month = jan,
doi = "10.1681/ASN.2015111224",
language = "English",
volume = "28",
pages = "230--241",
journal = "J AM SOC NEPHROL",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "1",

}

RIS

TY - JOUR

T1 - mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells

AU - Grahammer, Florian

AU - Ramakrishnan, Suresh K

AU - Rinschen, Markus M

AU - Larionov, Alexey A

AU - Syed, Maryam

AU - Khatib, Hazim

AU - Roerden, Malte

AU - Sass, Jörn Oliver

AU - Helmstaedter, Martin

AU - Osenberg, Dorothea

AU - Kühne, Lucas

AU - Kretz, Oliver

AU - Wanner, Nicola

AU - Jouret, Francois

AU - Benzing, Thomas

AU - Artunc, Ferruh

AU - Huber, Tobias B

AU - Theilig, Franziska

N1 - Copyright © 2016 by the American Society of Nephrology.

PY - 2017/1

Y1 - 2017/1

N2 - 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.

AB - 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.

KW - Animals

KW - Endocytosis

KW - Kidney Tubules, Proximal

KW - Mice

KW - Multiprotein Complexes

KW - Protein Transport

KW - TOR Serine-Threonine Kinases

KW - Journal Article

U2 - 10.1681/ASN.2015111224

DO - 10.1681/ASN.2015111224

M3 - SCORING: Journal article

C2 - 27297946

VL - 28

SP - 230

EP - 241

JO - J AM SOC NEPHROL

JF - J AM SOC NEPHROL

SN - 1046-6673

IS - 1

ER -