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Fission yeast tor1 functions in response to various stresses including nitrogen starvation, high osmolarity, and high
1Department of Chemistry, Faculty of Science, Shizuoka University, 836 Oya, Shizuoka, 422-8529, Japan.
Abstract:
A target of rapamycin (TOR) protein is a protein kinase that exerts cellular signal transduction to regulate cell growth in response to extracellular nutrient conditions. In the Schizosaccharomyces pombe genome database, there are two genes encoding TOR-related proteins, but their functions have not been analyzed. Here we report that one of the genes, referred to as tor1+, is required for sexual development induced by nitrogen starvation. Ste11 is a key transcription factor for the initiation of sexual development. The expression of ste11+ is normally regulated in tor1- cells; and overexpression of ste11+ hardly rescues the defect in fertility in tor1-. Upon nitrogen starvation, tor1+ cells promote two rounds of the cell cycle to become arrested at the G1 phase before initiation of sexual development. The tor1- cells do not promote such a cell cycle, suggesting that Tor1 is necessary for the response to nitrogen starvation. The tor1- cells show no growth or very slow growth under various stress conditions, including external high pH, high concentrations of salts or sorbitol, and high temperature. These results suggest that Tor1 is necessary for any response to a wide range of stresses. The vegetative growth of tor1- cells is inhibited by rapamycin, although tor1+ cells are resistant to the drug. The tor1- cells are hypersensitive to fluphenazine and cyclosporin A, which specifically inhibit calmodulin and calcineurin, respectively.
Insights
The target of rapamycin (TOR) protein Tor1 is essential for sexual development and stress response in Schizosaccharomyces pombe. Tor1 regulates cell cycle progression under nitrogen starvation, impacting fertility and survival under various environmental stresses.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Target of rapamycin (TOR) proteins are crucial kinases regulating cell growth based on nutrient availability.
- Two TOR-related genes exist in Schizosaccharomyces pombe, but their functions remain uncharacterized.
- Sexual development and stress responses are vital cellular processes influenced by nutrient and environmental cues.
Purpose of the Study:
- To investigate the function of the Schizosaccharomyces pombe tor1+ gene.
- To determine Tor1's role in sexual development and response to nutrient starvation.
- To analyze Tor1's involvement in cellular stress resistance.
Main Methods:
- Gene expression analysis of ste11+ in tor1- cells.
- Cell cycle analysis under nitrogen starvation.
- Phenotypic analysis of tor1- cells under various stress conditions (high pH, salt, sorbitol, temperature).
- Sensitivity assays using rapamycin, fluphenazine, and cyclosporin A.
Main Results:
- tor1+ is required for sexual development induced by nitrogen starvation.
- tor1- cells fail to arrest at the G1 phase after nitrogen starvation, unlike wild-type cells.
- tor1- cells exhibit impaired growth under diverse stress conditions, including osmotic, alkaline, and thermal stress.
- tor1- cells are sensitive to rapamycin, fluphenazine, and cyclosporin A, indicating Tor1's role in drug sensitivity.
Conclusions:
- Tor1 is essential for initiating sexual development in response to nitrogen starvation.
- Tor1 plays a critical role in regulating cell cycle progression during nutrient deprivation.
- Tor1 is indispensable for survival and growth under a broad spectrum of environmental stresses.
- Tor1 function is linked to pathways involving calmodulin and calcineurin.