Loss of the TOR Kinase Tor2 Mimics Nitrogen Starvation and Activates the Sexual Development Pathway in Fission Yeast

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2007 Jan 31

PMID 17261596

Citations 112

Authors

Tomohiko Matsuo

Yoko Otsubo

Jun Urano

Fuyuhiko Tamanoi

Masayuki Yamamoto

Affiliations

Soon will be listed here.

Abstract

Fission yeast has two TOR (target of rapamycin) kinases, namely Tor1 and Tor2. Tor1 is required for survival under stressed conditions, proper G(1) arrest, and sexual development. In contrast, Tor2 is essential for growth. To analyze the functions of Tor2, we constructed two temperature-sensitive tor2 mutants. Interestingly, at the restrictive temperature, these mutants mimicked nitrogen starvation by arresting the cell cycle in G(1) phase and initiating sexual development. Microarray analysis indicated that expression of nitrogen starvation-responsive genes was induced extensively when Tor2 function was suppressed, suggesting that Tor2 normally mediates a signal from the nitrogen source. As with mammalian and budding yeast TOR, we find that fission yeast TOR also forms multiprotein complexes analogous to TORC1 and TORC2. The raptor homologue, Mip1, likely forms a complex predominantly with Tor2, producing TORC1. The rictor/Avo3 homologue, Ste20, and the Avo1 homologue, Sin1, appear to form TORC2 mainly with Tor1 but may also bind Tor2. The Lst8 homologue, Wat1, binds to both Tor1 and Tor2. Our analysis shows, with respect to promotion of G(1) arrest and sexual development, that the loss of Tor1 (TORC2) and the loss of Tor2 (TORC1) exhibit opposite effects. This highlights an intriguing functional relationship among TOR kinase complexes in the fission yeast Schizosaccharomyces pombe.

Citing Articles

Proteomic and phosphoproteomic analyses reveal that TORC1 is reactivated by pheromone signaling during sexual reproduction in fission yeast.

Berard M, Merlini L, Martin S PLoS Biol. 2024; 22(12):e3002963.

PMID: 39705284 PMC: 11750111. DOI: 10.1371/journal.pbio.3002963.

The Greatwall-Endosulfine-PP2A/B55 pathway regulates entry into quiescence by enhancing translation of Elongator-tunable transcripts.

Encinar Del Dedo J, Suarez M, Lopez-San Segundo R, Vazquez-Bolado A, Sun J, Garcia-Blanco N Nat Commun. 2024; 15(1):10603.

PMID: 39638797 PMC: 11621810. DOI: 10.1038/s41467-024-55004-4.

Nitrogen starvation leads to TOR kinase-mediated downregulation of fatty acid synthesis in the algae Chlorella sorokiniana and Chlamydomonas reinhardtii.

Vijayan J, Alvarez S, Naldrett M, Morse W, Maliva A, Wase N BMC Plant Biol. 2024; 24(1):753.

PMID: 39107711 PMC: 11302099. DOI: 10.1186/s12870-024-05408-7.

Rapamycin-sensitive mechanisms confine the growth of fission yeast below the temperatures detrimental to cell physiology.

Morozumi Y, Mahayot F, Nakase Y, Soong J, Yamawaki S, Sofyantoro F iScience. 2024; 27(1):108777.

PMID: 38269097 PMC: 10805665. DOI: 10.1016/j.isci.2023.108777.

The Greatwall-Endosulfine-PP2A/B55 pathway controls entry into quiescence by promoting translation of Elongator-tuneable transcripts.

Encinar Del Dedo J, Lopez-San Segundo R, Vazquez-Bolado A, Sun J, Garcia-Blanco N, Suarez M Res Sq. 2023; .

PMID: 38105947 PMC: 10723533. DOI: 10.21203/rs.3.rs-3616701/v1.

References

Wilkinson M, Pino T, Tournier S, Buck V, Martin H, Christiansen J . Sin1: an evolutionarily conserved component of the eukaryotic SAPK pathway. EMBO J. 1999; 18(15):4210-21. PMC: 1171497. DOI: 10.1093/emboj/18.15.4210. View

Hilti N, Baumann D, Schweingruber A, BIGLER P, Schweingruber M . Gene ste20 controls amiloride sensitivity and fertility in Schizosaccharomyces pombe. Curr Genet. 1999; 35(6):585-92. DOI: 10.1007/s002940050456. View

Beck T, Hall M . The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature. 1999; 402(6762):689-92. DOI: 10.1038/45287. View

Hardwick J, Kuruvilla F, Tong J, Shamji A, Schreiber S . Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins. Proc Natl Acad Sci U S A. 1999; 96(26):14866-70. PMC: 24739. DOI: 10.1073/pnas.96.26.14866. View

Cardenas M, Cutler N, Lorenz M, Di Como C, Heitman J . The TOR signaling cascade regulates gene expression in response to nutrients. Genes Dev. 2000; 13(24):3271-9. PMC: 317202. DOI: 10.1101/gad.13.24.3271. View

Watanabe Y, Yamamoto M . Novel WD-repeat protein Mip1p facilitates function of the meiotic regulator Mei2p in fission yeast. Mol Cell Biol. 2000; 20(4):1234-42. PMC: 85253. DOI: 10.1128/MCB.20.4.1234-1242.2000. View

Mach K, Furge K, Albright C . Loss of Rhb1, a Rheb-related GTPase in fission yeast, causes growth arrest with a terminal phenotype similar to that caused by nitrogen starvation. Genetics. 2000; 155(2):611-22. PMC: 1461131. DOI: 10.1093/genetics/155.2.611. View

Komeili A, Wedaman K, OShea E, Powers T . Mechanism of metabolic control. Target of rapamycin signaling links nitrogen quality to the activity of the Rtg1 and Rtg3 transcription factors. J Cell Biol. 2000; 151(4):863-78. PMC: 2169436. DOI: 10.1083/jcb.151.4.863. View

Weisman R, Choder M . The fission yeast TOR homolog, tor1+, is required for the response to starvation and other stresses via a conserved serine. J Biol Chem. 2000; 276(10):7027-32. DOI: 10.1074/jbc.M010446200. View

10.

Li C, Wong W . Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc Natl Acad Sci U S A. 2001; 98(1):31-6. PMC: 14539. DOI: 10.1073/pnas.98.1.31. View

11.

Weisman R, Finkelstein S, Choder M . Rapamycin blocks sexual development in fission yeast through inhibition of the cellular function of an FKBP12 homolog. J Biol Chem. 2001; 276(27):24736-42. DOI: 10.1074/jbc.M102090200. View

12.

Kawai M, Nakashima A, Ueno M, USHIMARU T, Aiba K, Doi H . Fission yeast tor1 functions in response to various stresses including nitrogen starvation, high osmolarity, and high temperature. Curr Genet. 2001; 39(3):166-74. DOI: 10.1007/s002940100198. View

13.

Yang W, Tabancay Jr A, Urano J, Tamanoi F . Failure to farnesylate Rheb protein contributes to the enrichment of G0/G1 phase cells in the Schizosaccharomyces pombe farnesyltransferase mutant. Mol Microbiol. 2001; 41(6):1339-47. DOI: 10.1046/j.1365-2958.2001.02599.x. View

14.

Ochotorena I, Hirata D, Kominami K, Potashkin J, Sahin F, Gould K . Conserved Wat1/Pop3 WD-repeat protein of fission yeast secures genome stability through microtubule integrity and may be involved in mRNA maturation. J Cell Sci. 2001; 114(Pt 16):2911-20. DOI: 10.1242/jcs.114.16.2911. View

15.

Wood V, Gwilliam R, Rajandream M, LYNE M, Lyne R, Stewart A . The genome sequence of Schizosaccharomyces pombe. Nature. 2002; 415(6874):871-80. DOI: 10.1038/nature724. View

16.

Crespo J, Powers T, Fowler B, Hall M . The TOR-controlled transcription activators GLN3, RTG1, and RTG3 are regulated in response to intracellular levels of glutamine. Proc Natl Acad Sci U S A. 2002; 99(10):6784-9. PMC: 124480. DOI: 10.1073/pnas.102687599. View

17.

Matsumoto S, Bandyopadhyay A, Kwiatkowski D, Maitra U, Matsumoto T . Role of the Tsc1-Tsc2 complex in signaling and transport across the cell membrane in the fission yeast Schizosaccharomyces pombe. Genetics. 2002; 161(3):1053-63. PMC: 1462175. DOI: 10.1093/genetics/161.3.1053. View

18.

Mata J, Lyne R, Burns G, Bahler J . The transcriptional program of meiosis and sporulation in fission yeast. Nat Genet. 2002; 32(1):143-7. DOI: 10.1038/ng951. View

19.

Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo J, Bonenfant D . Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell. 2002; 10(3):457-68. DOI: 10.1016/s1097-2765(02)00636-6. View

20.

Nakashima A, Ueno M, Ushimaru T, Uritani M . Involvement of a CCAAT-binding complex in the expression of a nitrogen-starvation-specific gene, isp6+, in Schizosaccharomyces pombe. Biosci Biotechnol Biochem. 2002; 66(10):2224-7. DOI: 10.1271/bbb.66.2224. View