Opposite effects of tor1 and tor2 on nitrogen starvation responses in fission yeast.
The TOR protein kinases exhibit a conserved role in regulating cellular growth and proliferation. In the fission yeast two TOR homologs are present. tor1(+) is required for starvation and stress responses, while tor2(+) is essential. We report here that Tor2 depleted cells show a phenotype very similar to that of wild-type cells starved for nitrogen, including arrest at the G(1) phase of the cell cycle, induction of nitrogen-starvation-specific genes, and entrance into the sexual development pathway. The phenotype of tor2 mutants is in a striking contrast to the failure of tor1 mutants to initiate sexual development or arrest in G(1) under nitrogen starvation conditions. Tsc1 and Tsc2, the genes mutated in the human tuberous sclerosis complex syndrome, negatively regulate the mammalian TOR via inactivation of the GTPase Rheb. We analyzed the genetic relationship between the two TOR genes and the Schizosaccharomyces pombe orthologs of TSC1, TSC2, and Rheb. Our data suggest that like in higher eukaryotes, the Tsc1-2 complex negatively regulates Tor2. In contrast, the Tsc1-2 complex and Tor1 appear to work in parallel, both positively regulating amino acid uptake through the control of expression of amino acid permeases. Additionally, either Tsc1/2 or Tor1 are required for growth on a poor nitrogen source such as proline. Mutants lacking Tsc1 or Tsc2 are highly sensitive to rapamycin under poor nitrogen conditions, suggesting that the function of Tor1 under such conditions is sensitive to rapamycin. We discuss the complex genetic interactions between tor1(+), tor2(+), and tsc1/2(+) and the implications for rapamycin sensitivity in tsc1 or tsc2 mutants.
Weisman
Ronit
R
Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. ronitt@post.tau.ac.il
Roitburg
Irina
I
Schonbrun
Miriam
M
Harari
Rona
R
Kupiec
Martin
M
D026905:Amino Acid Transport Systems / Q000378:metabolism; D015152:Blotting, Northern; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D005434:Flow Cytometry; D015966:Gene Expression Regulation, Fungal; D007930:Leucine / Q000378:metabolism; D009584:Nitrogen / Q000172:deficiency*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D012098:Reproduction / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012568:Schizosaccharomyces / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D020123:Sirolimus
D026905:Amino Acid Transport Systems; D017931:DNA Primers; D007930:Leucine; D009584:Nitrogen; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D029702:Schizosaccharomyces pombe Proteins; D020123:Sirolimus; C471572:Tsc1 protein, S pombe; C471573:Tsc2 protein, S pombe; C523461:Tor1 protein, S pombe; C513100:tor2 protein, S pombe