Li Jinmei, Yan Gonghong, Liu Sichi, Jiang Tong, Zhong Mingming, Yuan Wenjie, Chen Shaoxian, Zheng Yin, Jiang Yong, Jiang Yu
Department of Pathophysiology, Southern Medical University, Guangzhou, China.
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Mol Microbiol. 2017 Dec;106(6):938-948. doi: 10.1111/mmi.13858. Epub 2017 Oct 26.
In yeast target of rapamycin complex 1 (TORC1) and Tap42-associated phosphatases regulate expression of genes involved in nitrogen limitation response and the nitrogen discrimination pathway. However, it remains unclear whether TORC1 and the phosphatases are required for sensing nitrogen conditions. Utilizing temperature sensitive mutants of tor2 and tap42, we examined the role of TORC1 and Tap42 in nuclear entry of Gln3, a key transcription factor in yeast nitrogen metabolism, in response to changes in nitrogen conditions. Our data show that TORC1 is essential for Gln3 nuclear entry upon nitrogen limitation and downshift in nitrogen quality. However, Tap42-associated phosphatases are required only under nitrogen limitation condition. In cells grown in poor nitrogen medium, the nitrogen permease reactivator kinase (Npr1) inhibits TORC1 activity and alters its association with Tap42, rendering Tap42-associated phosphatases unresponsive to nitrogen limitation. These findings demonstrate a direct role for TORC1 and Tap42-associated phosphatases in sensing nitrogen conditions and unveil an Npr1-dependent mechanism that controls TORC1 and the phosphatases in response to changes in nitrogen quality.
在酵母中，雷帕霉素靶蛋白复合物1（TORC1）和与Tap42相关的磷酸酶调节参与氮限制反应和氮鉴别途径的基因表达。然而，TORC1和这些磷酸酶是否为感知氮条件所必需仍不清楚。利用tor2和tap42的温度敏感突变体，我们研究了TORC1和Tap42在酵母氮代谢关键转录因子Gln3响应氮条件变化进入细胞核过程中的作用。我们的数据表明，在氮限制和氮质量下降时，TORC1对于Gln3进入细胞核至关重要。然而，只有在氮限制条件下才需要与Tap42相关的磷酸酶。在低氮培养基中生长的细胞中，氮通透酶再激活激酶（Npr1）抑制TORC1活性并改变其与Tap42的结合，使与Tap42相关的磷酸酶对氮限制无反应。这些发现证明了TORC1和与Tap42相关的磷酸酶在感知氮条件方面的直接作用，并揭示了一种依赖Npr1的机制，该机制可根据氮质量的变化控制TORC1和磷酸酶。
