Lysosomal accumulation of mTOR is enhanced by rapamycin

Histochem Cell Biol. 2010 Dec;134(6):537-44. doi: 10.1007/s00418-010-0759-x. Epub 2010 Nov 10.

Abstract

The mammalian target of rapamycin (mTOR) is a key regulator of cell growth that integrates signals from growth factors and nutrients. Recent studies have shown that an mTOR-containing complex, mTORC1, is targeted to lysosomes in the presence of amino acids and activated by Rheb GTPase resident in that compartment. In this study, we found that treatment with the mTOR inhibitors rapamycin and Torin1 significantly enhanced lysosomal accumulation of mTOR and Raptor. This phenomenon was not observed in the absence of amino acids but was restored upon addition of L-leucine or protein synthesis inhibitors. mTOR was not concentrated in autophagosomes that were induced by rapamycin. These results suggest that the lysosome harbors both active and inactive forms of mTOR in the presence of amino acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Amino Acids / pharmacology
  • Animals
  • Autophagy / physiology
  • COS Cells
  • Chlorocebus aethiops
  • HeLa Cells
  • Humans
  • Leucine / pharmacology
  • Lysosomes / drug effects
  • Lysosomes / metabolism*
  • Mechanistic Target of Rapamycin Complex 1
  • Monomeric GTP-Binding Proteins / metabolism
  • Multiprotein Complexes
  • Naphthyridines / pharmacology
  • Neuropeptides / metabolism
  • Proteins / metabolism
  • Ras Homolog Enriched in Brain Protein
  • Regulatory-Associated Protein of mTOR
  • Sirolimus / pharmacology*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one
  • Adaptor Proteins, Signal Transducing
  • Amino Acids
  • Multiprotein Complexes
  • Naphthyridines
  • Neuropeptides
  • Proteins
  • RHEB protein, human
  • RPTOR protein, human
  • Ras Homolog Enriched in Brain Protein
  • Regulatory-Associated Protein of mTOR
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Monomeric GTP-Binding Proteins
  • Leucine
  • Sirolimus