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Gene-targeted Random Mutagenesis to Select Heterochromatin-destabilizing Proteasome Mutants in Fission Yeast
07:18

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Published on: May 15, 2018

Rapamycin specifically interferes with the developmental response of fission yeast to starvation

R Weisman1, M Choder, Y Koltin

  • 1Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Tel Aviv University, Israel. ronitt@post.tau.ac.il

Journal of Bacteriology
|October 23, 1997
PubMed

Insights

Rapamycin inhibits sexual development in Schizosaccharomyces pombe under starvation conditions, not vegetative growth. This effect is linked to the cyclic AMP pathway and Ras1 signaling, suggesting a novel mechanism for rapamycin

Area of Science:

  • * Molecular Biology
  • * Mycology
  • * Genetics

Background:

  • * Rapamycin, an immunosuppressive macrolide, inhibits T lymphocytes and Saccharomyces cerevisiae growth by blocking cell cycle progression.
  • * Rapamycin is known to affect fungal growth, but its specific impact on the sexual development of Schizosaccharomyces pombe was unclear.

Purpose of the Study:

  • * To investigate the effect of rapamycin on the vegetative and sexual development of Schizosaccharomyces pombe.
  • * To identify the signal transduction pathway involved in rapamycin's action in this yeast species.

Main Methods:

  • * Comparative analysis of rapamycin's effect on vegetative growth versus starvation-induced sexual development in Schizosaccharomyces pombe.
  • * Genetic screening of mutant strains (adenylate cyclase deletion, pka1 mutation, pat1-114 mutation, ras1+ overexpression) to identify pathways involved in rapamycin response.
  • * Functional analysis of ras1Val17 (activated allele) in antagonizing rapamycin's effects.

Main Results:

  • * Rapamycin did not inhibit vegetative growth but significantly suppressed sexual development (mating and sporulation) in Schizosaccharomyces pombe under starvation.
  • * The drug's inhibitory effect on sexual development was not observed in strains with deleted adenylate cyclase or mutated cyclic AMP-dependent protein kinase (pka1).
  • * Expression of an activated Ras1 allele (ras1Val17) antagonized rapamycin's effect, restoring mating competence.

Conclusions:

  • * Rapamycin inhibits sexual development in Schizosaccharomyces pombe via a pathway involving cyclic AMP and Ras1 signaling, distinct from its effects on vegetative growth.
  • * The findings reveal a novel mechanism of rapamycin action in yeast, highlighting its role in regulating developmental transitions under nutrient stress.
  • * This study provides genetic insights into the regulation of sexual development in fission yeast and the specific targets of rapamycin in this process.

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