Abstract：
The mechanistic target of rapamycin complex 1 (mTORC1) regulates metabolism and cell growth in response to nutrient levels. Dysregulation of mTORC1 results in a broad spectrum of diseases. Glucose is the primary energy supply of cells, and therefore, glucose levels must be accurately conveyed to mTORC1 through highly responsive signaling mechanisms to control mTORC1 activity. Here, we report that glucose-induced mTORC1 activation is regulated by O-GlcNAcylation of Raptor, a core component of mTORC1, in HEK293T cells. Mechanistically, O-GlcNAcylation of Raptor at threonine 700 facilitates the interactions between Raptor and Rag GTPases and promotes the translocation of mTOR to the lysosomal surface, consequently activating mTORC1. In addition, we show that AMPK-mediated phosphorylation of Raptor suppresses Raptor O-GlcNAcylation and inhibits Raptor-Rags interactions. Our findings reveal an exquisitely controlled mechanism, which suggests how glucose coordinately regulates cellular anabolism and catabolism.
摘要：
雷帕霉素复合物1(mTORC1)的机制靶标响应于营养水平调节代谢和细胞生长。mTORC1的失调导致广谱的疾病。葡萄糖是细胞的主要能量供应，因此,必须通过高度响应的信号机制将葡萄糖水平准确地传递给mTORC1以控制mTORC1的活性。这里,我们报道了葡萄糖诱导的mTORC1激活受Raptor的O-GlcNAcylation调节，HEK293T细胞中mTORC1的核心组分。机械上,Raptor在苏氨酸700处的O-GlcNAcylation促进Raptor和RagGTPases之间的相互作用，并促进mTOR易位到溶酶体表面，从而激活mTORC1。此外,我们表明AMPK介导的Raptor磷酸化抑制RaptorO-GlcNAcylation并抑制Raptor-Rags相互作用。我们的发现揭示了一种精确控制的机制，这表明葡萄糖如何协调调节细胞合成代谢和分解代谢。
