Mammalian/mechanistic target of rapamycin (mTOR) complexes are essential for cell proliferation, growth, differentiation, and survival. mTORC1 hyperactivation occurs in the tuberous sclerosis complex (TSC). mTORC1 localizes to the surface of lysosomes, where Rheb activates it. However, mTOR was also found on the endoplasmic reticulum (ER) and Golgi apparatus (GA). Recent studies showed that the same inputs regulate ER-to-GA cargo transport and mTORC1 (e.g., the level of amino acids or energy status of the cell). Nonetheless, it remains unknown whether mTOR contributes to the regulation of cargo passage through the secretory pathway. The retention using selective hooks (RUSH) approach was used to image movement of model cargo (VSVg) between the ER and GA in various cell lines in which mTOR complexes were inhibited. We also investigated VSVg trafficking in TSC patient fibroblasts. We found that mTOR inhibition led to the overall enhancement of VSVg transport through the secretory pathway in PC12 cells and primary human fibroblasts. Also, in TSC1-deficient cells, VSVg transport was enhanced. Altogether, these data indicate the involvement of mTOR in the regulation of ER-to-GA cargo transport and suggest that impairments in exocytosis may be an additional cellular process that is disturbed in TSC.

中文翻译：

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mTOR 控制特定细胞类型中 VSVg 的内质网 - 高尔基体运输

哺乳动物/雷帕霉素机械靶标 (mTOR) 复合物对细胞增殖、生长、分化和存活至关重要。mTORC1 过度活化发生在结节性硬化症 (TSC) 中。mTORC1 定位于溶酶体的表面，在那里 Rheb 激活它。然而，在内质网 (ER) 和高尔基体 (GA) 上也发现了 mTOR。最近的研究表明，相同的输入调节 ER 到 GA 的货物运输和 mTORC1（例如，细胞的氨基酸水平或能量状态）。尽管如此，mTOR 是否有助于通过分泌途径调节货物通道仍然未知。使用选择性钩子 (RUSH) 方法的保留用于对 mTOR 复合物受到抑制的各种细胞系中 ER 和 GA 之间模型货物 (VSVg) 的移动进行成像。我们还调查了 TSC 患者成纤维细胞中的 VSVg 贩运。我们发现 mTOR 抑制导致 VSVg 通过 PC12 细胞和原代人成纤维细胞中的分泌途径转运的整体增强。此外，在 TSC1 缺陷细胞中，VSVg 转运得到增强。总之，这些数据表明 mTOR 参与了 ER 到 GA 货物运输的调节，并表明胞吐作用的障碍可能是 TSC 中受到干扰的额外细胞过程。