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The Late Endosome is Essential for mTORC1 Signaling

The multisubunit mTORC1 complex integrates signals from growth factors and nutrients to regulate protein synthesis, cell growth, and autophagy. To examine how endocytic trafficking might be involved in nutrient regulation of mTORC1, we perturbed specific endocytic trafficking pathways and measured m...

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Detalles Bibliográficos
Autores principales: Flinn, Rory J., Yan, Ying, Goswami, Sumanta, Parker, Peter J., Backer, Jonathan M.
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828969/
https://www.ncbi.nlm.nih.gov/pubmed/20053679
http://dx.doi.org/10.1091/mbc.E09-09-0756
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author Flinn, Rory J.
Yan, Ying
Goswami, Sumanta
Parker, Peter J.
Backer, Jonathan M.
author_facet Flinn, Rory J.
Yan, Ying
Goswami, Sumanta
Parker, Peter J.
Backer, Jonathan M.
author_sort Flinn, Rory J.
collection PubMed
description The multisubunit mTORC1 complex integrates signals from growth factors and nutrients to regulate protein synthesis, cell growth, and autophagy. To examine how endocytic trafficking might be involved in nutrient regulation of mTORC1, we perturbed specific endocytic trafficking pathways and measured mTORC1 activity using S6K1 as a readout. When early/late endosomal conversion was blocked by either overexpression of constitutively active Rab5 (Rab5CA) or knockdown of the Rab7 GEF hVps39, insulin- and amino acid–stimulated mTORC1/S6K1 activation were inhibited, and mTOR localized to hybrid early/late endosomes. Inhibition of other stages of endocytic trafficking had no effect on mTORC1. Overexpression of Rheb, which activates mTOR independently of mTOR localization, rescued mTORC1 signaling in cells expressing Rab5CA, whereas hyperactivation of endogenous Rheb in TSC2−/− MEFs did not. These data suggest that integrity of late endosomes is essential for amino acid– and insulin-stimulated mTORC1 signaling and that blocking the early/late endosomal conversion prevents mTOR from interacting with Rheb in the late endosomal compartment.
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spelling pubmed-28289692010-05-16 The Late Endosome is Essential for mTORC1 Signaling Flinn, Rory J. Yan, Ying Goswami, Sumanta Parker, Peter J. Backer, Jonathan M. Mol Biol Cell Articles The multisubunit mTORC1 complex integrates signals from growth factors and nutrients to regulate protein synthesis, cell growth, and autophagy. To examine how endocytic trafficking might be involved in nutrient regulation of mTORC1, we perturbed specific endocytic trafficking pathways and measured mTORC1 activity using S6K1 as a readout. When early/late endosomal conversion was blocked by either overexpression of constitutively active Rab5 (Rab5CA) or knockdown of the Rab7 GEF hVps39, insulin- and amino acid–stimulated mTORC1/S6K1 activation were inhibited, and mTOR localized to hybrid early/late endosomes. Inhibition of other stages of endocytic trafficking had no effect on mTORC1. Overexpression of Rheb, which activates mTOR independently of mTOR localization, rescued mTORC1 signaling in cells expressing Rab5CA, whereas hyperactivation of endogenous Rheb in TSC2−/− MEFs did not. These data suggest that integrity of late endosomes is essential for amino acid– and insulin-stimulated mTORC1 signaling and that blocking the early/late endosomal conversion prevents mTOR from interacting with Rheb in the late endosomal compartment. The American Society for Cell Biology 2010-03-01 /pmc/articles/PMC2828969/ /pubmed/20053679 http://dx.doi.org/10.1091/mbc.E09-09-0756 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
Flinn, Rory J.
Yan, Ying
Goswami, Sumanta
Parker, Peter J.
Backer, Jonathan M.
The Late Endosome is Essential for mTORC1 Signaling
title The Late Endosome is Essential for mTORC1 Signaling
title_full The Late Endosome is Essential for mTORC1 Signaling
title_fullStr The Late Endosome is Essential for mTORC1 Signaling
title_full_unstemmed The Late Endosome is Essential for mTORC1 Signaling
title_short The Late Endosome is Essential for mTORC1 Signaling
title_sort late endosome is essential for mtorc1 signaling
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828969/
https://www.ncbi.nlm.nih.gov/pubmed/20053679
http://dx.doi.org/10.1091/mbc.E09-09-0756
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