TORC1 signaling is governed by two negative regulators in fission yeast
Ning Ma1, Qingbin Liu, Lili Zhang
1Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Abstract:
The target of rapamycin (TOR) is a highly conserved protein kinase that regulates cell growth and metabolism. Here we performed a genome-wide screen to identify negative regulators of TOR complex 1 (TORC1) in Schizosaccharomyces pombe by isolating mutants that phenocopy Δtsc2, in which TORC1 signaling is known to be up-regulated. We discovered that Δnpr2 displayed similar phenotypes to Δtsc2 in terms of amino acid uptake defects and mislocalization of the Cat1 permease. However, Δnpr2 and Δtsc2 clearly showed different phenotypes in terms of rapamycin supersensitivity and Isp5 transcription upon various treatments. Furthermore, we showed that Tor2 controls amino acid homeostasis at the transcriptional and post-transcriptional levels. Our data reveal that both Npr2 and Tsc2 negatively regulate TORC1 signaling, and Npr2, but not Tsc2, may be involved in the feedback loop of a nutrient-sensing pathway.
Insights
Researchers identified Npr2 as a negative regulator of the target of rapamycin (TOR) pathway in yeast. Unlike Tsc2, Npr2 appears to be involved in nutrient sensing feedback loops, impacting cell growth and metabolism.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The target of rapamycin (TOR) pathway is a crucial regulator of cell growth, metabolism, and nutrient sensing.
- TOR complex 1 (TORC1) signaling is tightly controlled, and its dysregulation is implicated in various cellular processes.
- Identifying negative regulators of TORC1 is essential for understanding cellular homeostasis.
Purpose of the Study:
- To conduct a genome-wide screen in Schizosaccharomyces pombe to identify novel negative regulators of TORC1 signaling.
- To characterize the function of identified regulators by comparing their phenotypes to known regulators like Tsc2.
- To elucidate the specific roles of Npr2 and Tsc2 in TORC1 pathway regulation and nutrient sensing.
Main Methods:
- Genome-wide screening of Schizosaccharomyces pombe mutants.
- Phenotypic analysis including amino acid uptake, Cat1 permease localization, rapamycin sensitivity, and Isp5 transcription.
- Comparative analysis of mutant phenotypes (e.g., Δnpr2 vs. Δtsc2).
Main Results:
- A genome-wide screen identified Npr2 as a negative regulator of TORC1 signaling in S. pombe.
- Δnpr2 mutants exhibited phenotypes similar to Δtsc2 mutants, including amino acid uptake defects and Cat1 permease mislocalization.
- Distinct phenotypes were observed between Δnpr2 and Δtsc2 mutants regarding rapamycin supersensitivity and Isp5 transcription, suggesting differential roles.
- Tor2 was shown to regulate amino acid homeostasis at both transcriptional and post-transcriptional levels.
- Npr2, but not Tsc2, appears to be involved in the feedback loop of a nutrient-sensing pathway.
Conclusions:
- Both Npr2 and Tsc2 function as negative regulators of TORC1 signaling in S. pombe.
- Npr2 plays a role in regulating amino acid homeostasis and may participate in nutrient-sensing feedback mechanisms.
- Tsc2 and Npr2 exhibit both overlapping and distinct functions in TORC1 pathway regulation.
- These findings contribute to a deeper understanding of the complex regulatory network governing cell growth and metabolism.
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