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Research Article
The S. pombe CDK5 ortholog Pef1 regulates sexual differentiation through control of the TORC1 pathway and autophagy
Shinya Matsuda, Ushio Kikkawa, Haruka Uda, Akio Nakashima
Journal of Cell Science 2020 133: jcs247817 doi: 10.1242/jcs.247817 Published 9 September 2020
Shinya Matsuda
1Biosignal Research Center, Kobe University, Kobe, 657-8501, Japan
2Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan
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  • ORCID record for Shinya Matsuda
  • For correspondence: s-matsuda@u-shizuoka-ken.ac.jp anakashima@person.kobe-u.ac.jp
Ushio Kikkawa
1Biosignal Research Center, Kobe University, Kobe, 657-8501, Japan
3Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, Kobe, 657-8501, Japan
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Haruka Uda
3Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, Kobe, 657-8501, Japan
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Akio Nakashima
1Biosignal Research Center, Kobe University, Kobe, 657-8501, Japan
3Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, Kobe, 657-8501, Japan
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  • ORCID record for Akio Nakashima
  • For correspondence: s-matsuda@u-shizuoka-ken.ac.jp anakashima@person.kobe-u.ac.jp

Handling Editor: John Heath

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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.

Footnotes

  • Competing interests

    The authors declare no competing or financial interests.

  • Author contributions

    Conceptualization: S.M., A.N.; Methodology: S.M., H.U., A.N.; Software: S.M., U.K., A.N.; Validation: S.M., U.K., H.U., A.N.; Formal analysis: S.M., H.U.; Investigation: S.M., H.U.; Resources: S.M., U.K., H.U., A.N.; Data curation: S.M., H.U.; Writing - original draft: S.M.; Writing - review & editing: U.K., A.N.; Visualization: S.M.; Supervision: U.K., A.N.; Project administration: S.M., A.N.; Funding acquisition: S.M., U.K., A.N.

  • Funding

    This study was supported in part by the Japan Society for the Promotion of Science (JSPS) KAKENHI grant numbers 19K15751 (S.M.) and 26440053 (A.N.).

  • Supplementary information

    Supplementary information available online at https://jcs.biologists.org/lookup/doi/10.1242/jcs.247817.supplemental

  • Received April 23, 2020.
  • Accepted July 20, 2020.
  • © 2020. Published by The Company of Biologists Ltd
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Keywords

  • Sexual differentiation
  • Pef1
  • CDK5
  • TORC1
  • Autophagy
  • Cyclin

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Research Article
The S. pombe CDK5 ortholog Pef1 regulates sexual differentiation through control of the TORC1 pathway and autophagy
Shinya Matsuda, Ushio Kikkawa, Haruka Uda, Akio Nakashima
Journal of Cell Science 2020 133: jcs247817 doi: 10.1242/jcs.247817 Published 9 September 2020
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Research Article
The S. pombe CDK5 ortholog Pef1 regulates sexual differentiation through control of the TORC1 pathway and autophagy
Shinya Matsuda, Ushio Kikkawa, Haruka Uda, Akio Nakashima
Journal of Cell Science 2020 133: jcs247817 doi: 10.1242/jcs.247817 Published 9 September 2020

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