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V-ATPase/mTOR signaling regulates megalin-mediated apical endocytosis

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V-ATPase/mTOR signaling regulates megalin-mediated apical endocytosis. / Gleixner, Eva Maria; Canaud, Guillaume; Hermle, Tobias; Guida, Maria Clara; Kretz, Oliver; Helmstädter, Martin; Huber, Tobias B; Eimer, Stefan; Terzi, Fabiola; Simons, Matias.

In: CELL REP, Vol. 8, No. 1, 10.07.2014, p. 10-9.

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

Harvard

Gleixner, EM, Canaud, G, Hermle, T, Guida, MC, Kretz, O, Helmstädter, M, Huber, TB, Eimer, S, Terzi, F & Simons, M 2014, 'V-ATPase/mTOR signaling regulates megalin-mediated apical endocytosis', CELL REP, vol. 8, no. 1, pp. 10-9. https://doi.org/10.1016/j.celrep.2014.05.035

APA

Gleixner, E. M., Canaud, G., Hermle, T., Guida, M. C., Kretz, O., Helmstädter, M., Huber, T. B., Eimer, S., Terzi, F., & Simons, M. (2014). V-ATPase/mTOR signaling regulates megalin-mediated apical endocytosis. CELL REP, 8(1), 10-9. https://doi.org/10.1016/j.celrep.2014.05.035

Vancouver

Gleixner EM, Canaud G, Hermle T, Guida MC, Kretz O, Helmstädter M et al. V-ATPase/mTOR signaling regulates megalin-mediated apical endocytosis. CELL REP. 2014 Jul 10;8(1):10-9. https://doi.org/10.1016/j.celrep.2014.05.035

Bibtex

@article{4d6e22521cf54599b4b549fcf790aec4,
title = "V-ATPase/mTOR signaling regulates megalin-mediated apical endocytosis",
abstract = "mTOR kinase is a master growth regulator that can be stimulated by multiple signals, including amino acids and the lysosomal small GTPase Rheb. Recent studies have proposed an important role for the V-ATPase in the sensing of amino acids in the lysosomal lumen. Using the Drosophila wing as a model epithelium, we show here that the V-ATPase is required for Rheb-dependent epithelial growth. We further uncover a positive feedback loop for the control of apical protein uptake that depends on V-ATPase/mTOR signaling. This feedback loop includes Rheb-dependent transcriptional regulation of the multiligand receptor Megalin, which itself is required for Rheb-induced endocytosis. In addition, we provide evidence that long-term mTOR inhibition with rapamycin in mice causes reduction of Megalin levels and proteinuria in the proximal tubular epithelium of the kidney. Thus, our findings unravel a homeostatic mechanism that allows epithelial cells to promote protein uptake under normal conditions and to prevent uptake in lysosomal stress conditions.",
keywords = "Animals, Drosophila, Drosophila Proteins, Endocytosis, Epithelium, Feedback, Physiological, Low Density Lipoprotein Receptor-Related Protein-2, Male, Mice, Mice, Inbred C57BL, Monomeric GTP-Binding Proteins, Neuropeptides, Proteinuria, Signal Transduction, TOR Serine-Threonine Kinases, Vacuolar Proton-Translocating ATPases, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Gleixner, {Eva Maria} and Guillaume Canaud and Tobias Hermle and Guida, {Maria Clara} and Oliver Kretz and Martin Helmst{\"a}dter and Huber, {Tobias B} and Stefan Eimer and Fabiola Terzi and Matias Simons",
note = "Copyright {\textcopyright} 2014 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2014",
month = jul,
day = "10",
doi = "10.1016/j.celrep.2014.05.035",
language = "English",
volume = "8",
pages = "10--9",
journal = "CELL REP",
issn = "2211-1247",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - V-ATPase/mTOR signaling regulates megalin-mediated apical endocytosis

AU - Gleixner, Eva Maria

AU - Canaud, Guillaume

AU - Hermle, Tobias

AU - Guida, Maria Clara

AU - Kretz, Oliver

AU - Helmstädter, Martin

AU - Huber, Tobias B

AU - Eimer, Stefan

AU - Terzi, Fabiola

AU - Simons, Matias

N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2014/7/10

Y1 - 2014/7/10

N2 - mTOR kinase is a master growth regulator that can be stimulated by multiple signals, including amino acids and the lysosomal small GTPase Rheb. Recent studies have proposed an important role for the V-ATPase in the sensing of amino acids in the lysosomal lumen. Using the Drosophila wing as a model epithelium, we show here that the V-ATPase is required for Rheb-dependent epithelial growth. We further uncover a positive feedback loop for the control of apical protein uptake that depends on V-ATPase/mTOR signaling. This feedback loop includes Rheb-dependent transcriptional regulation of the multiligand receptor Megalin, which itself is required for Rheb-induced endocytosis. In addition, we provide evidence that long-term mTOR inhibition with rapamycin in mice causes reduction of Megalin levels and proteinuria in the proximal tubular epithelium of the kidney. Thus, our findings unravel a homeostatic mechanism that allows epithelial cells to promote protein uptake under normal conditions and to prevent uptake in lysosomal stress conditions.

AB - mTOR kinase is a master growth regulator that can be stimulated by multiple signals, including amino acids and the lysosomal small GTPase Rheb. Recent studies have proposed an important role for the V-ATPase in the sensing of amino acids in the lysosomal lumen. Using the Drosophila wing as a model epithelium, we show here that the V-ATPase is required for Rheb-dependent epithelial growth. We further uncover a positive feedback loop for the control of apical protein uptake that depends on V-ATPase/mTOR signaling. This feedback loop includes Rheb-dependent transcriptional regulation of the multiligand receptor Megalin, which itself is required for Rheb-induced endocytosis. In addition, we provide evidence that long-term mTOR inhibition with rapamycin in mice causes reduction of Megalin levels and proteinuria in the proximal tubular epithelium of the kidney. Thus, our findings unravel a homeostatic mechanism that allows epithelial cells to promote protein uptake under normal conditions and to prevent uptake in lysosomal stress conditions.

KW - Animals

KW - Drosophila

KW - Drosophila Proteins

KW - Endocytosis

KW - Epithelium

KW - Feedback, Physiological

KW - Low Density Lipoprotein Receptor-Related Protein-2

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Monomeric GTP-Binding Proteins

KW - Neuropeptides

KW - Proteinuria

KW - Signal Transduction

KW - TOR Serine-Threonine Kinases

KW - Vacuolar Proton-Translocating ATPases

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.celrep.2014.05.035

DO - 10.1016/j.celrep.2014.05.035

M3 - SCORING: Journal article

C2 - 24953654

VL - 8

SP - 10

EP - 19

JO - CELL REP

JF - CELL REP

SN - 2211-1247

IS - 1

ER -