A PP2A-B55-Mediated Crosstalk between TORC1 and TORC2 Regulates the Differentiation Response in Fission Yeast.
A PP2A-B55-Mediated Crosstalk between TORC1 and TORC2 Regulates the Differentiation Response in Fission Yeast.
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TORC1和TORC2之间的PP2A-B55介导的串扰调节裂变酵母中的分化反应。
DOI：
10.1016/j.cub.2016.11.037
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发表时间：
2017-01-23
期刊：
影响因子：
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通讯作者：
Lopez-Aviles S
中科院分区：
文献类型：
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作者：
Martín R;Portantier M;Chica N;Nyquist-Andersen M;Mata J;Lopez-Aviles S
细胞外信号调节细胞命运，这主要是通过参与特定的转录程序来实现的。TORC 1和TORC 2复合物介导营养线索与细胞行为的整合，但它们的相互作用知之甚少。在这里，我们使用裂变酵母，以调查磷酸酶活性如何参与这种相互作用的开关期间，从增殖到性分化。我们发现PP 2A-B55 Pab 1的缺失增强了分化特异性基因的表达，并导致过早接合。pab 1缺失导致与TORC 1失活相似的转录谱，并且pab 1的缺失克服了过表达TORC 1的细胞中分化基因的抑制。重要的是，我们表明这种效应是由增加的TORC 2-AKT（Gad 8）信号传导介导的。在营养丰富的条件下，PP 2A-B55 Pab 1使Gad 8 Ser 546去磷酸化，抑制其活性。相反，饥饿时TORC 1失活导致PP 2A-B55 Pab 1通过长城-硫丹途径失活。这导致Gad 8的激活和分化的承诺。因此，PP 2A-B55 Pab 1使得两种TOR复合物之间的串扰能够控制响应于营养可用性的细胞命运决定。PP 2A-B55 Pab 1调节裂殖酵母细胞的分化反应PP 2A-B55 Pab 1使TORC 1和TORC 2之间的串扰TORC 1有利于PP 2A-B55 Pab 1活性，以防止Gad 8的过度磷酸化TORC 1失活导致PP 2A-B55 Pab 1抑制，Gad 8的激活和分化TORC 1和TORC 2在裂殖酵母的分化反应中起相反的作用。在这里，马丁等人。表明PP 2A-B55 Pab 1协调这两个模块的活动以响应氮的可用性，从而将营养状态与细胞命运决定联系起来。
Extracellular cues regulate cell fate, and this is mainly achieved through the engagement of specific transcriptional programs. The TORC1 and TORC2 complexes mediate the integration of nutritional cues to cellular behavior, but their interplay is poorly understood. Here, we use fission yeast to investigate how phosphatase activity participates in this interplay during the switch from proliferation to sexual differentiation. We find that loss of PP2A-B55Pab1 enhances the expression of differentiation-specific genes and leads to premature conjugation. pab1 deletion brings about a transcriptional profile similar to TORC1 inactivation, and deletion of pab1 overcomes the repression of differentiation genes in cells overexpressing TORC1. Importantly, we show that this effect is mediated by an increased TORC2-AKT (Gad8) signaling. Under nutrient-rich conditions, PP2A-B55Pab1 dephosphorylates Gad8 Ser546, repressing its activity. Conversely, TORC1 inactivation upon starvation leads to the inactivation of PP2A-B55Pab1 through the Greatwall-Endosulfin pathway. This results in the activation of Gad8 and the commitment to differentiation. Thus, PP2A-B55Pab1 enables a crosstalk between the two TOR complexes that controls cell-fate decisions in response to nutrient availability. PP2A-B55Pab1 regulates the differentiation response of fission yeast cells PP2A-B55Pab1 enables a crosstalk between TORC1 and TORC2 TORC1 favors PP2A-B55Pab1 activity to prevent the hyperphosphorylation of Gad8 TORC1 inactivation leads to PP2A-B55Pab1 inhibition, activation of Gad8, and differentiation TORC1 and TORC2 play opposite roles in the differentiation response of fission yeast. Here, Martin et al. show that PP2A-B55Pab1 coordinates the activities of these two modules in response to nitrogen availability, thus connecting nutritional status to cell-fate decisions.