Fission yeast Tor2 links nitrogen signals to cell proliferation and acts downstream of the Rheb GTPase
Fission yeast Tor2 links nitrogen signals to cell proliferation and acts downstream of the Rheb GTPase
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DOI：
10.1111/j.1365-2443.2006.01025.x
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发表时间：
2006-12-01
期刊：
影响因子：
2.1
通讯作者：
Toda, Takashi
中科院分区：
文献类型：
--
作者：
Uritani, Masahiro;Hidaka, Hidetoshi;Toda, Takashi
雷帕霉素的靶点Tor在细胞生长和代谢中起着关键作用。酵母含有两种相关的蛋白质，Tor 1和Tor 2。在裂殖酵母中，Tor 1是正常生长所必需的，但在各种应激条件下参与氨基酸摄取和细胞存活。相比之下，Tor 2是细胞增殖所必需的;然而，其生理功能仍然未知。在这里，我们通过创建温度敏感（tor 2（ts））突变体来表征裂殖酵母Tor 2的作用。值得注意的是，我们已经发现tor 2（ts）模拟氮饥饿反应，因为突变体显示了许多通常只在氮剥夺时诱导的表型。这些包括G1期细胞周期停滞与小细胞大小，诱导自噬和性别分化的承诺。相比之下，tor 1 Delta tor 2（ts）双突变细胞显示出不同的表型，因为在没有G1停滞的情况下，细胞停止分裂，细胞大小正常。Tor 2与保守的Rhb 1/GTb 3相互作用。有趣的是，过量表达rhb 1（+）或缺失Rhb 1-GAP编码的tsc 2（+）能够拯救tor 1突变体的应激敏感表型，这意味着Tor 1和Tor 2在不利环境下的细胞存活中也具有共同的功能。我们建议，Tor 1和Tor 2参与营养传感和应激反应途径的确证和独立的角色。
The target of rapamycin (Tor) plays a pivotal role in cell growth and metabolism. Yeast contains two related proteins, Tor1 and Tor2. In fission yeast, Tor1 is dispensable for normal growth but is involved in amino acid uptake and cell survival under various stress conditions. In contrast, Tor2 is essential for cell proliferation; however, its physiological function remains unknown. Here we characterize the roles of fission yeast Tor2 by creating temperature sensitive (tor2(ts)) mutants. Remarkably, we have found that tor2(ts) mimics nitrogen starvation responses, because the mutant displays a number of phenotypes that are normally induced only on nitrogen deprivation. These include G1 cell-cycle arrest with a small cell size, induction of autophagy and commitment to sexual differentiation. By contrast, tor1 Delta tor2(ts) double mutant cells show distinct phenotypes, as the cells cease division with normal cell size in the absence of G1 arrest. Tor2 physically interacts with the conserved Rhb1/GTPase. Intriguingly, over-expression of rhb1(+) or deletion of Rhb1-GAP-encoding tsc2(+) is capable of rescuing stress-sensitive phenotypes of the tor1 mutant, implying that Tor1 and Tor2 also share functions in cell survival under adverse environment. We propose that Tor1 and Tor2 are involved in both corroborative and independent roles in nutrient sensing and stress response pathways.