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Lysosomal accumulation of mTOR is enhanced by rapamycin

Yuki Ohsaki1, Michitaka Suzuki, Yuki Shinohara

  • 1Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan. yohsaki@med.nagoya-u.ac.jp

Histochemistry and Cell Biology
|November 11, 2010
PubMed

Insights

Mammalian target of rapamycin (mTOR) inhibitors like rapamycin increase mTOR complex accumulation in lysosomes. This lysosomal localization of mTOR occurs with amino acids and is reversed by their absence.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The mammalian target of rapamycin (mTOR) pathway is crucial for regulating cell growth, responding to growth factors and nutrients.
  • mTOR complex 1 (mTORC1) localizes to lysosomes, where it is activated by Rheb GTPase in response to amino acids.

Purpose of the Study:

  • To investigate the effect of mTOR inhibitors on the lysosomal localization of mTOR and its associated proteins.
  • To understand the role of amino acids and protein synthesis in regulating mTOR localization.

Main Methods:

  • Treatment of cells with mTOR inhibitors (rapamycin, Torin1).
  • Analysis of mTOR and Raptor localization using cell imaging techniques.
  • Manipulation of amino acid availability and protein synthesis.

Main Results:

  • Rapamycin and Torin1 treatment significantly increased the accumulation of mTOR and Raptor in lysosomes.
  • This lysosomal accumulation was dependent on the presence of amino acids.
  • Re-addition of L-leucine or inhibition of protein synthesis restored lysosomal mTOR accumulation.
  • mTOR did not accumulate in rapamycin-induced autophagosomes.

Conclusions:

  • Lysosomes serve as a compartment for both active and inactive forms of mTOR, particularly in the presence of amino acids.
  • Amino acid availability and protein synthesis are key regulators of mTOR localization to lysosomes.

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