Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Histochem Cell Biol. 2010 Dec;134(6):537-44. doi: 10.1007/s00418-010-0759-x. Epub 2010 Nov 10.
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.
哺乳动物雷帕霉素靶蛋白(mTOR)是细胞生长的关键调节剂,它整合了来自生长因子和营养物质的信号。最近的研究表明,在氨基酸存在的情况下,一种包含 mTOR 的复合物 mTORC1 被靶向到溶酶体,并被驻留在该隔室中的 Rheb GTPase 激活。在这项研究中,我们发现用 mTOR 抑制剂雷帕霉素和 Torin1 处理可显著增强 mTOR 和 Raptor 在溶酶体中的积累。在没有氨基酸的情况下没有观察到这种现象,但添加 L-亮氨酸或蛋白质合成抑制剂后即可恢复。mTOR 没有集中在由雷帕霉素诱导的自噬体中。这些结果表明,在氨基酸存在的情况下,溶酶体中既存在有活性的 mTOR 形式,也存在无活性的 mTOR 形式。
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