Distinctive Responses to Nitrogen Starvation in the Dominant Active Mutants of the Fission Yeast Rheb GTPase
Distinctive Responses to Nitrogen Starvation in the Dominant Active Mutants of the Fission Yeast Rheb GTPase
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DOI：
10.1534/genetics.109.105379
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发表时间：
2009-10-01
期刊：
影响因子：
3.3
通讯作者：
Matsumoto, Tomohiro
中科院分区：
文献类型：
--
作者：
Murai, Tomoka;Nakase, Yukiko;Matsumoto, Tomohiro
Rheb是一种从人类到酵母都保守的Ras样小GTPase，控制Tor激酶，并在取决于细胞外条件的细胞生长调节中发挥核心作用。Rhb 1（Rheb的裂殖酵母同源物）调节氨基酸摄取以及对氮饥饿的反应。在这项研究中，我们产生了两个突变体，rhb 1-DA 4和rhb 1-DA 8，并对其进行了遗传学表征。Ras样GTP酶定义的G1盒内的V17 A突变负责rhb 1-DA 4，开关II结构域内的Q52 R176 F负责rhb 1-DA 8。在裂殖酵母中，有两个事件减数分裂起始基因mei 2（+）的诱导和细胞分裂而细胞不生长是对氮饥饿的典型反应。在富氮条件下，Rheb刺激Tor激酶，Tor激酶反过来抑制对氮饥饿的反应。虽然氨基酸的吸收被阻止由rhb 1-DA 4和rhb 1-DA 8在一个占主导地位的方式，氮饥饿的反应，防止只有由rhb 1-DA 4。因此，rhb 1-DA 8允许对Rheb依赖性信号级联进行遗传分析。我们推测，信号级联可能分支低于Rhb 1或Tort和调节氨基酸的吸收和响应氮饥饿独立。
Rheb, a Ras-like small GTPase conserved from human to yeast, controls Tor kinase and plays a central role in the regulation of Cell growth depending on extracellular Conditions. Rhb1 (a fission yeast homolog of Rheb) regulates amino acid uptake as well as response to nitrogen starvation. In this study, we generated two mutants, rhb1-DA4 and rhb1-DA8, and characterised them genetically. The V17A mutation within the G1 box defined for the Ras-like GTPases was responsible for rhb1-DA4 and Q52R176F within the switch II domain for rhb1-DA8. In fission yeast, two events-the induction of the meiosis-initiating gene mei2(+) and cell division without cell growth-are a typical response to nitrogen starvation. Under nitrogen-rich conditions, Rheb stimulates Tor kinase, which, in turn, suppresses the response to nitrogen starvation. While amino acid uptake was prevented by both rhb1-DA4 and rhb1-DA8 in a dominant fashion, the response to nitrogen starvation was prevented only by rhb1-DA4. rhb1-DA8 thereby allowed genetic dissection of the Rheb-dependent signaling cascade. We postulate that the signaling cascade may branch below Rhb1 or Tort and regulate the amino acid uptake and response to nitrogen starvation independently.