Skip to main content
Log in

A starvation-specific serine protease gene, isp6 +, is involved in both autophagy and sexual development in Schizosaccharomyces pombe

  • Research Article
  • Published:
Current Genetics Aims and scope Submit manuscript

Abstract

Schizosaccharomyces pombe isp6 + gene encodes a vacuolar serine protease, which is specifically induced during nitrogen starvation. An isp6-disruption mutant, isp6Δ, grew normally under normal conditions but was defective in large-scale protein degradation during nitrogen starvation, a hallmark of autophagy. Vacuoles are the organelles for such drastic protein degradation but those of isp6Δ were apparently aberrant. isp6Δ was infertile under nitrogen source-free conditions with poor expression of ste11 +, a gene critical for sexual development. A protein kinase A-disruption mutant, pka1Δ, is prone to sexual development because expression of ste11 + is derepressed. However, isp6Δpka1Δ still showed defects in ste11 + expression and sexual development under nitrogen source-free conditions. isp6Δ and isp6Δpka1Δ were able to initiate sexual development to produce spores when only a small amount of a nitrogen source was present. Pat1 protein kinase negatively controls meiosis, and a temperature-sensitive mutant of pat1, pat1-114, initiates meiosis irrespective of ploidy at the restrictive temperature. However, isp6Δpat1-114 did not start meiosis under nitrogen source-free conditions even at the restrictive temperature. These observations suggest that isp6 + contributes to sexual development by providing a nitrogen source through autophagy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Abe H, Shimoda C (2000) Autoregulated expression of Schizosaccharomyces pombe meiosis-specific transcription factor Mei4 and a genome-wide search for its target genes. Genetics 154:1497–1508

    CAS  PubMed  Google Scholar 

  • Beach D, Rodgers L, Gould J (1985) RAN1 + controls the transition from mitotic division to meiosis in fission yeast. Curr Genet 10:297–311

    Article  CAS  PubMed  Google Scholar 

  • Brazer SC, Williams HP, Chappell TG, Cande WZ (2000) A fission yeast kinesin affects Golgi membrane recycling. Yeast 16:149–166

    Article  CAS  PubMed  Google Scholar 

  • Chen D, Toone WM, Mata J, Lyne R, Burns G, Kivinen K, Brazma A, Jones N, Bähler J (2003) Global transcriptional responses of fission yeast to environmental stress. Mol Biol Cell 14:214–229

    Article  CAS  PubMed  Google Scholar 

  • Davey J (1998) Fusion of a fission yeast. Yeast 14:1529–1566

    Article  CAS  PubMed  Google Scholar 

  • DeVoti J, Seydoux G, Beach D, McLeod M (1991) Interaction between ran1 + protein kinase and cAMP dependent protein kinase as negative regulators of fission yeast meiosis. EMBO J 10:3759–3768

    CAS  PubMed  Google Scholar 

  • Egel R (1989) Mating-type genes. meiosis, and sporulation. In: Nasim A, Young P, Johnson BF (eds) Molecular biology of the fission yeast. Academic, San Diego, pp 31–73

    Google Scholar 

  • Epple UD, Suriapranata I, Eskelinen EL, Thumm M (2001) Aut5/Cvt17p, a putative lipase essential for disintegration of autophagic bodies inside the vacuole. J Bacteriol 183:5942–5955

    Article  CAS  PubMed  Google Scholar 

  • Grimm C, Kohli J, Murray J, Maundrell K (1988) Genetic engineering of Schizosaccharomyces pombe: a system for gene disruption and replacement using the ura4 + gene as a selectable marker. Mol Gen Genet 215:81–86

    Article  CAS  PubMed  Google Scholar 

  • Horie S, Watanabe Y, Tanaka K, Nishiwaki S, Fujioka H, Abe H, Yamamoto M, Shimoda C (1998) The Schizosaccharomyces pombe mei4 + gene encodes a meiosis-specific transcription factor containing a forkhead DNA-binding domain. Mol Cell Biol 18:2118–2129

    CAS  PubMed  Google Scholar 

  • Higuchi T, Watanabe Y, Yamamoto M (2002) Protein kinase A regulates sexual development and gluconeogenesis through phosphorylation of the Zn finger transcriptional activator Rst2p in fission yeast. Mol Cell Biol 22:1–11

    Article  CAS  PubMed  Google Scholar 

  • Iino Y, Yamamoto M (1985) Negative control for the initiation of meiosis in Schizosaccharomyces pombe. Proc Natl Acad Sci USA 82:2447–2451

    Article  CAS  PubMed  Google Scholar 

  • Iino Y, Hiramine Y, Yamamoto M (1995) The role of cdc2 and other genes in meiosis in Schizosaccharomyces pombe. Genetics 140:1235–1245

    CAS  PubMed  Google Scholar 

  • Kanoh J, Watanabe Y, Ohsugi M, Iino Y, Yamamoto M (1996) Schizosaccharomyces pombe gad7 + encodes a phosphoprotein with a bZIP1 domain, which is required for proper G1 arrest and gene expression under nitrogen starvation. Genes Cells 1:391–408

    Article  CAS  PubMed  Google Scholar 

  • Kato T, Okazaki K, Murakami H, Stettler S, Fants PA, Okayama H (1996) Stress signal, mediated by a Hog1-like MAP kinase, controls sexual development in fission yeast. FEBS Lett 378:207–212

    Article  CAS  PubMed  Google Scholar 

  • Kawai M, Nakashima A, Ueno M, Ushimaru T, Aiba K, Doi H, Uritani M (2001) Fission yeast Tor1 functions in response to various stresses including nitrogen starvation, high osmolarity, and high temperature. Curr Genet 39:166–174

    Article  CAS  PubMed  Google Scholar 

  • Kim J, Klionsky DJ (2000) Autophagy, cytoplasm-to-vacuole targeting pathway, and pexophagy in yeast and mammalian cells. Annu Rev Biochem 69:303–342

    Article  CAS  PubMed  Google Scholar 

  • Kunitomo H, Sugimoto A, Wilkinson CR, Yamamoto M (1995) Schizosaccharomyces pombe pac2 + controls the onset of sexual development via a pathway independent of the cAMP cascade. Curr Genet 28:32–38

    Article  CAS  PubMed  Google Scholar 

  • Kunitomo H, Higuchi T, Iino Y, Yamamoto M (2000) A zinc-finger protein, Rst2p, regulates transcription of the fission yeast ste11 + gene, which encodes a pivotal transcription factor for sexual development. Mol Biol Cell 11:3205–3217

    CAS  PubMed  Google Scholar 

  • Maeda T, Watanabe Y, Kunitomo H, Yamamoto M (1994) Cloning of the pka1 gene encoding the catalytic subunit of the cAMP-dependent protein kinase in Schizosaccharomyces pombe. J Biol Chem 269:9632–9637

    CAS  PubMed  Google Scholar 

  • Maundrell K (1993) Thiamine-repressible expression vectors pREP and pRIP for fission yeast. Gene 123:127–130

    Article  CAS  PubMed  Google Scholar 

  • McLeod M, Beach D (1988) A specific inhibitor of the ran1 + protein kinase regulates entry into meiosis in Schizosaccharomyces pombe. Nature 332:509–514

    Article  CAS  PubMed  Google Scholar 

  • Moehle CM, Tizard R, Lemmon SK, Smart J, Jones EW (1987) Protease B of the lysosomelike vacuole of the yeast Saccharomyces cerevisiae is homologous to the subtilisin family of serine proteases. Mol Cell Biol 7:4390–4399

    CAS  PubMed  Google Scholar 

  • Moreno S, Klar A, Nurse P (1991) Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol 194:795–823

    Article  CAS  PubMed  Google Scholar 

  • Morishita M, Shimoda C (2000) Positioning of medial actin rings affected by eccentrically located nuclei in a fission yeast mutant having large vacuoles. FEMS Microbiol Lett 188:63–67

    Article  CAS  PubMed  Google Scholar 

  • Nakashima A, Ueno M, Ushimaru T, Uritani M (2002a) Involvement of a CCAAT-binding complex in the expression of a nitrogen-starvation-specific gene isp6 +, in Schizosaccharomyces pombe. Biosci Biotechnol Biochem 66:2224–2227

    Article  CAS  Google Scholar 

  • Nakashima A, Yoshida M, Nakayama K, Kato-Furuno A, Ueno M, Ushimaru T, Uritani M (2002b) Genes for a nuclease and a protease are involved in the drastic decrease in cellular RNA amount in fission yeast cells during nitrogen starvation. J Biochem 131:391–398

    CAS  Google Scholar 

  • Ohmiya R, Yamada H, Kato C, Aiba H, Mizuno T (2000) The Prr1 response regulator is essential for sexual development in fission yeast. Mol Gen Genet 264:441–451

    Article  CAS  PubMed  Google Scholar 

  • Ohsumi Y (2001) Molecular dissection of autophagy: two ubiquitin-like systems. Nat Rev Mol Cell Biol 2:211–216

    Article  CAS  PubMed  Google Scholar 

  • Okazaki K, Okazaki N, Kume K, Jinno S, Tanaka K, Okayama H (1990) High-frequency transformation method and library transducing vectors for cloning mammalian cDNAs by trans-complementation of Schizosaccharomyces pombe. Nucleic Acids Res 18:6485–6489

    Article  CAS  PubMed  Google Scholar 

  • Sato S, Suzuki H, Widyastuti U, Hotta Y, Tabata S (1994) Identification and characterization of genes induced during sexual differentiation in Schizosaccharomyces pombe. Curr Genet 26:31–37

    Article  CAS  PubMed  Google Scholar 

  • Shiozaki K, Russell P (1996) Conjugation, meiosis, and the osmotic stress response are regulated by Spc1 kinase through Atf1 transcription factor in fission yeast. Genes Dev 10:2276–2288

    Article  CAS  PubMed  Google Scholar 

  • Shiozaki K, Shiozaki M, Russell P (1998) Heat stress activates fission yeast Spc1/Sty1 MAPK by a MEKK-independent mechanism. Mol Biol Cell 9:1339–1349

    CAS  PubMed  Google Scholar 

  • Stiefel J, Wang L, Kelly DA, Janoo RT, Seitz J, Whitehall SK, Hoffman CS (2004) Suppressors of an adenylate cyclase deletion in the fission yeast Schizosaccharomyces pombe. Eukaryot Cell 3:610–619

    Article  CAS  PubMed  Google Scholar 

  • Su SS, Tanaka Y, Samejima I, Tanaka K, Yanagida M (1996) A nitrogen starvation-induced dormant G0 state in fission yeast: the establishment from uncommitted G1 state and its delay for return to proliferation. J Cell Sci 109:1347–1357

    CAS  PubMed  Google Scholar 

  • Sugimoto A, Iino Y, Maeda T, Watanabe Y, Yamamoto M (1991) Schizosaccharomyces pombe ste11 + encodes a transcription factor with an HMG motif that is a critical regulator of sexual development. Genes Dev 5:1990–1999

    Article  CAS  PubMed  Google Scholar 

  • Suriapranata I, Epple UD, Bernreuther D, Bredschneider M, Sovarasteanu K, Thumm M (2000) The breakdown of autophagic vesicles inside the vacuole depends on Aut4p. J Cell Sci 113:4025–4033

    CAS  PubMed  Google Scholar 

  • Takeda T, Toda T, Kominami K, Kohnosu A, Yanagida M, Jones N (1995) Schizosaccharomyces pombe atf1 + encodes a transcription factor required for sexual development and entry into stationary phase. EMBO J 14:6193–6208

    CAS  PubMed  Google Scholar 

  • Takeshige K, Baba M, Tsuboi S, Noda T, Ohsumi Y (1992) Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol 119:301–311

    Article  CAS  PubMed  Google Scholar 

  • Teichert U, Mechler B, Müller H, Wolf DH (1989) Lysosomal (vacuolar) proteinases of yeast are essential catalysts for protein degradation, differentiation, and cell survival. J Biol Chem 264:16037–16045

    CAS  PubMed  Google Scholar 

  • Tsukada M, Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333:169–174

    Article  CAS  PubMed  Google Scholar 

  • Ueno M, Kurokawa R, Renauld H, Watanabe K, Ushimaru T, Uritani M, Yoshinaga K, Hiraoka Y (2001) Schizosaccharomyces pombe taf1 + is required for nitrogen starvation-induced sexual development and for entering the dormant G0 state. Curr Genet 38:307–313

    Article  CAS  PubMed  Google Scholar 

  • Vida TA, Emr SD (1995) A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast. J Cell Biol 128:779–792

    Article  CAS  PubMed  Google Scholar 

  • Watanabe Y, Yamamoto M (1996) Schizosaccharomyces pombe pcr1 + encodes a CREB/ATF protein involved in regulation of gene expression for sexual development. Mol Cell Biol 16:704–711

    CAS  PubMed  Google Scholar 

  • Weisman R, Choder M (2001) The fission yeast TOR homolog, tor1 +, is required for the response to starvation and other stresses via a conserved serine. J Biol Chem 276:7027–7032

    Article  CAS  PubMed  Google Scholar 

  • Wilkinson MG, Samuels M, Takeda T, Toone WM, Shieh JC, Toda T, Millar JB, Jones N (1996) The Atf1 transcription factor is a target for the Sty1 stress-activated MAP kinase pathway in fission yeast. Genes Dev 10:2289–2301

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto M, Imai Y, Watanabe Y (1997) Mating and sporulation in Schizosaccharomyces pombe. In: Broach JR, Jones EW (eds) The molecular and cellular biology of the yeast Saccharomyces. Cell cycle and cell biology, vol 3. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 1037–1106

  • Zubenko GS, Mitchell AP, Jones EW (1979) Septum formation, cell division, and sporulation in mutants of yeast deficient in protease B. Proc Natl Acad Sci USA 76:2395–2399

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank M. Yamamoto, Y. Watanabe, K. Tanaka, and K. Okazaki for providing the strains and T. Toda, K. Takegawa, and H. Masuda for critical reading of the manuscript. This work was supported in part by the Sasakawa Scientific Research Grant from the Japan Science Society.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Masahiro Uritani.

Additional information

Communicated by C. Hoffman

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakashima, A., Hasegawa, T., Mori, S. et al. A starvation-specific serine protease gene, isp6 +, is involved in both autophagy and sexual development in Schizosaccharomyces pombe . Curr Genet 49, 403–413 (2006). https://doi.org/10.1007/s00294-006-0067-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00294-006-0067-0

Keywords

Navigation