The S. pombe CDK5 ortholog Pef1 regulates sexual differentiation through control of the TORC1 pathway and autophagy
The S. pombe CDK5 ortholog Pef1 regulates sexual differentiation through control of the TORC1 pathway and autophagy
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DOI：
10.1242/jcs.247817
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发表时间：
2020-01
影响因子：
4
通讯作者：
S. Matsuda;U. Kikkawa;Haruka Uda;A. Nakashima
中科院分区：
文献类型：
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作者：
S. Matsuda;U. Kikkawa;Haruka Uda;A. Nakashima
在pombe Schizosaccharomyces中，性别分化是应对环境变化的一般生存策略，这是由TORC1失活引发的。然而，裂变酵母中TORC1调控的机制仍然知之甚少。在本研究中，我们发现Pef1是哺乳动物CDK5的同源基因，通过正向调节TORC1活性来调节性别分化的启动。相反，在氮饥饿反应的早期阶段，pef1的缺失会导致自噬的激活和随后的TORC1的过度再激活。这种过度的TORC1再激活导致Ste11-Mei2通路的沉默和交配缺陷。此外，我们发现pef1基因与tsc1和tsc2相互作用以调控TORC1，并与三个周期蛋白Clg1、Pas1和Psl1物理相互作用。clg1和pas1的双重缺失在氮饥饿期间促进自噬和TORC1的激活，类似于pef1Δ细胞中所见的情况。总的来说，我们的工作表明，Pef1-Clg1和Pef1-Pas1复合物通过控制TSC-TORC1途径和自噬来调节性别分化的启动。摘要：在裂变酵母中，性别分化对于在环境变化中生存至关重要。我们发现Pef1通过控制TORC1途径和自噬来调节性别分化的启动。
ABSTRACT In Schizosaccharomyces pombe, a general strategy for survival in response to environmental changes is sexual differentiation, which is triggered by TORC1 inactivation. However, mechanisms of TORC1 regulation in fission yeast remain poorly understood. In this study, we found that Pef1, which is an ortholog of mammalian CDK5, regulates the initiation of sexual differentiation through positive regulation of TORC1 activity. Conversely, deletion of pef1 leads to activation of autophagy and subsequent excessive TORC1 reactivation during the early phases of the nitrogen starvation response. This excessive TORC1 reactivation results in the silencing of the Ste11-Mei2 pathway and mating defects. Additionally, we found that pef1 genetically interacts with tsc1 and tsc2 for TORC1 regulation, and physically interacts with three cyclins, Clg1, Pas1 and Psl1. The double deletion of clg1 and pas1 promotes activation of autophagy and TORC1 during nitrogen starvation, similar to what is seen in pef1Δ cells. Overall, our work suggests that Pef1–Clg1 and Pef1–Pas1 complexes regulate initiation of sexual differentiation through control of the TSC–TORC1 pathway and autophagy. Summary: In fission yeast, sexual differentiation is important for survival in environmental changes. We found that Pef1 regulates initiation of sexual differentiation through control of the TORC1 pathway and autophagy.