The late endosome is essential for mTORC1 signaling

Rory J. Flinn, Ying Yan, Sumanta Goswami, Peter J. Parker, Jonathan M. Backer

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)833-841
Number of pages9
JournalMolecular Biology of the Cell
Volume21
Issue number5
DOIs
StatePublished - Mar 1 2010

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Endosomes
Insulin
Food
Essential Amino Acids
Autophagy
mechanistic target of rapamycin complex 1
Intercellular Signaling Peptides and Proteins
Amino Acids
Growth
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

The late endosome is essential for mTORC1 signaling. / Flinn, Rory J.; Yan, Ying; Goswami, Sumanta; Parker, Peter J.; Backer, Jonathan M.

In: Molecular Biology of the Cell, Vol. 21, No. 5, 01.03.2010, p. 833-841.

Research output: Contribution to journalArticle

Flinn, Rory J. ; Yan, Ying ; Goswami, Sumanta ; Parker, Peter J. ; Backer, Jonathan M. / The late endosome is essential for mTORC1 signaling. In: Molecular Biology of the Cell. 2010 ; Vol. 21, No. 5. pp. 833-841.
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