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.
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Acknowledgments
We thank Drs. David Sabatini (Whitehead Institute for Biomedical Research) and Tamotsu Yoshimori (Osaka University) for the generous gift of Torin1 and the GFP-LC3 expression vector, respectively, and Ms. Tsuyako Tatematsu and Dr. Jinglei Cheng for excellent technical assistance. This work was supported by Grants-in-Aid for Scientific Research, the Global COE Program “Integrated Molecular Medicine for Neuronal and Neoplastic Disorders” of the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese Government (to YO, TF), and research grants from Kazato Research Foundation and Takeda Science Foundation (to YO).
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Ohsaki, Y., Suzuki, M., Shinohara, Y. et al. Lysosomal accumulation of mTOR is enhanced by rapamycin. Histochem Cell Biol 134, 537–544 (2010). https://doi.org/10.1007/s00418-010-0759-x
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DOI: https://doi.org/10.1007/s00418-010-0759-x