The TOR and EGO protein complexes orchestrate microautophagy in yeast
The TOR and EGO protein complexes orchestrate microautophagy in yeast
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DOI：
10.1016/j.molcel.2005.05.020
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发表时间：
2005-07-01
期刊：
影响因子：
16
通讯作者：
De Virgillo, C
中科院分区：
文献类型：
--
作者：
Dubouloz, F;Deloche, O;De Virgillo, C
酿酒酵母中对雷帕霉素敏感的TOR信号通路积极控制细胞生长以响应营养供应。因此，TOR耗竭或雷帕霉素治疗导致细胞进入静止生长阶段。虽然这一过程已被详细阐明，但人们对从静止状态向扩散状态的转变知之甚少。在这里，我们描述了RAS相关GTP酶中RAGA亚家族的一个保守成员，GTR2，它与Ego1和Ego3一起作用于空泡膜相关蛋白复合体，以确保适当地退出雷帕霉素诱导的生长停滞。我们证明，EGO复合体与TOR一起，积极地调节微自噬，从而抵消雷帕霉素诱导的大量宏自噬介导的膜向空泡膜的内流。此外，对EGO复合体的大规模遗传分析证实了起源于液泡膜的生长控制机制的存在，并确定氨基酸谷氨酰胺是TOR信号中的关键代谢物。
The rapamycin-sensitive TOR signaling pathway in Saccharomyces cerevisiae positively controls cell growth in response to nutrient availability. Accordingly, TOR depletion or rapamycin treatment causes regulated entry of cells into a quiescent growth phase. Although this process has been elucidated in considerable detail, the transition from quiescence back to proliferation is poorly understood. Here, we describe the identification of a conserved member of the RagA subfamily of Ras-related GTPases, Gtr2, which acts in a vacuolar membrane-associated protein complex together with Ego1 and Ego3 to ensure proper exit from rapamycin-induced growth arrest. We demonstrate that the EGO complex, in conjunction with TOR, positively regulates microautophagy, thus counterbalancing the massive rapamycin-induced, macroautophagy-mediated membrane influx toward the vacuolar membrane. Moreover, large-scale genetic analyses of the EGO complex confirm the existence of a growth control mechanism originating at the vacuolar membrane and pinpoint the amino acid glutamine as a key metabolite in TOR signaling.