Fission yeast Tor2 links nitrogen signals to cell proliferation and acts downstream of the Rheb GTPase.
The target of rapamycin (Tor) plays a pivotal role in cell growth and metabolism. Yeast contains two related proteins, Tor1 and Tor2. In fission yeast, Tor1 is dispensable for normal growth but is involved in amino acid uptake and cell survival under various stress conditions. In contrast, Tor2 is essential for cell proliferation; however, its physiological function remains unknown. Here we characterize the roles of fission yeast Tor2 by creating temperature sensitive (tor2(ts)) mutants. Remarkably, we have found that tor2(ts) mimics nitrogen starvation responses, because the mutant displays a number of phenotypes that are normally induced only on nitrogen deprivation. These include G1 cell-cycle arrest with a small cell size, induction of autophagy and commitment to sexual differentiation. By contrast, tor1Deltator2(ts) double mutant cells show distinct phenotypes, as the cells cease division with normal cell size in the absence of G1 arrest. Tor2 physically interacts with the conserved Rhb1/GTPase. Intriguingly, over-expression of rhb1(+) or deletion of Rhb1-GAP-encoding tsc2(+) is capable of rescuing stress-sensitive phenotypes of the tor1 mutant, implying that Tor1 and Tor2 also share functions in cell survival under adverse environment. We propose that Tor1 and Tor2 are involved in both corroborative and independent roles in nutrient sensing and stress response pathways.
Uritani
Masahiro
M
Department of Chemistry, Faculty of Science, Shizuoka University, 836 Oya Suruga-ku, Shizuoka 422-8529, Japan. scmurit@ipc.shizuoka.ac.jp
Hidaka
Hidetoshi
H
Hotta
Yukari
Y
Ueno
Masaru
M
Ushimaru
Takashi
T
Toda
Takashi
T
D000595:Amino Acid Sequence; D017209:Apoptosis; D049109:Cell Proliferation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D005800:Genes, Fungal; D008969:Molecular Sequence Data; D009154:Mutation; D009584:Nitrogen / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013696:Temperature
D020558:GTP Phosphohydrolases; D009584:Nitrogen; D019869:Phosphatidylinositol 3-Kinases; D029702:Schizosaccharomyces pombe Proteins; C513100:tor2 protein, S pombe