Multiple functions of ergosterol in the fission yeast Schizosaccharomyces pombe

Microbiology. 2008 Mar;154(Pt 3):830-841. doi: 10.1099/mic.0.2007/011155-0.

Abstract

Sterols are a major class of membrane lipids in eukaryotes. In Schizosaccharomyces pombe, sterol 24-C-methyltransferase (Erg6p), C-8 sterol isomerase (Erg2p), C-5 sterol desaturase (Erg31p, Erg32p), C-22 sterol desaturase (Erg5p) and C-24 (28) sterol reductase (Sts1p/Erg4p) have been predicted, but not yet determined, to catalyse a sequence of reactions from zymosterol to ergosterol. Disruption mutants of these genes were unable to synthesize ergosterol, and most were tolerant to the polyene drugs amphotericin B and nystatin. Disruption of erg31(+) or erg32(+) did not cause ergosterol deficiency or tolerance to polyene drugs, indicating that the two C-5 sterol desaturases have overlapping functions. GFP-tagged DRM (detergent-resistant membrane)-associated protein Pma1p localized to the plasma membrane in ergDelta mutants. DRM fractionation revealed that the association between Pma1-GFP and DRM was weakened in erg6Delta but not in other erg mutants. Several GFP-tagged plasma membrane proteins were tested, and an amino acid permease homologue, SPBC359.03c, was found to mislocalize to intracellular punctate structures in the ergDelta mutants. These results indicate that these proteins are responsible for ergosterol biosynthesis in fission yeast, similar to the situation in Saccharomyces cerevisiae. Furthermore, in fission yeast, ergosterol is important for plasma membrane structure and function and for localization of plasma membrane proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems / analysis
  • Amphotericin B / pharmacology
  • Antifungal Agents / pharmacology
  • Cell Fractionation
  • Drug Resistance, Fungal / genetics
  • Enzymes / genetics
  • Enzymes / metabolism*
  • Ergosterol / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Deletion
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Membrane Proteins / analysis
  • Mutagenesis, Insertional
  • Nystatin / pharmacology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Schizosaccharomyces / chemistry
  • Schizosaccharomyces / drug effects
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces / genetics

Substances

  • Amino Acid Transport Systems
  • Antifungal Agents
  • Enzymes
  • Fungal Proteins
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • Nystatin
  • Green Fluorescent Proteins
  • Amphotericin B
  • Ergosterol