Ragulator 是 Rag GTPases 的鸟苷酸交换因子 (GEF)，可将氨基酸水平信号传递给 mTORC1。
Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1.
机构信息
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Nine Cambridge Center, Cambridge, MA 02142, USA.
出版信息
Cell. 2012 Sep 14;150(6):1196-208. doi: 10.1016/j.cell.2012.07.032.
The mTOR Complex 1 (mTORC1) pathway regulates cell growth in response to numerous cues, including amino acids, which promote mTORC1 translocation to the lysosomal surface, its site of activation. The heterodimeric RagA/B-RagC/D GTPases, the Ragulator complex that tethers the Rags to the lysosome, and the v-ATPase form a signaling system that is necessary for amino acid sensing by mTORC1. Amino acids stimulate the binding of guanosine triphosphate to RagA and RagB but the factors that regulate Rag nucleotide loading are unknown. Here, we identify HBXIP and C7orf59 as two additional Ragulator components that are required for mTORC1 activation by amino acids. The expanded Ragulator has nucleotide exchange activity toward RagA and RagB and interacts with the Rag heterodimers in an amino acid- and v-ATPase-dependent fashion. Thus, we provide mechanistic insight into how mTORC1 senses amino acids by identifying Ragulator as a guanine nucleotide exchange factor (GEF) for the Rag GTPases.
mTOR 复合物 1（mTORC1）途径可响应多种信号（包括氨基酸）调节细胞生长，这些信号促进 mTORC1 易位到溶酶体表面，这是其激活的部位。 RagA/B-RagC/D GTP 酶的异源二聚体、将 Rag 与溶酶体连接的 Ragulator 复合物以及 v-ATP 酶形成了一个信号系统，该系统对于 mTORC1 对氨基酸的感应是必需的。氨基酸刺激 RagA 和 RagB 结合鸟嘌呤三磷酸（GTP），但调节 Rag 核苷酸加载的因素尚不清楚。在这里，我们确定 HBXIP 和 C7orf59 是 Ragulator 的另外两个组成部分，它们对于氨基酸激活 mTORC1 是必需的。扩展的 Ragulator 对 RagA 和 RagB 具有核苷酸交换活性，并以氨基酸和 v-ATP 酶依赖的方式与 Rag 异源二聚体相互作用。因此，我们通过鉴定 Ragulator 作为 Rag GTP 酶的鸟嘌呤核苷酸交换因子（GEF），为 mTORC1 通过识别氨基酸提供了机制见解。
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