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Chapter 11 : Function and Regulation of Adhesin Gene Families in Saccharomyces cerevisiae, Candida albicans, and Candida glabrata
Category: Fungi and Fungal Pathogenesis
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In fungi, the cell wall plays a primary role contributing to the structural integrity of the cell; in addition to this structural role, the cell wall is, by definition, the interface between the yeast and the environment. This chapter examines the overlapping and divergent function and regulation of some surface glycoprotein gene families in Saccharomyces cerevisiae and its pathogenic cousins Candida glabrata and Candida albicans. S. cerevisiae, C. albicans, and C. glabrata encode a variety of glycosylphosphatidylinositol-linked cell wall proteins (GPI-CWPs) that play accessory roles, functioning primarily as adhesins, facilitating yeast-yeast interactions or yeast adherence to a variety of surfaces. Analysis of adhesin gene regulation in S. cerevisiae and in Candida species has revealed significant overlap in the signals that induce transcription of these gene families as well as the mechanistic basis for that regulation. Analysis of FLO gene transcription reveals unexpected complexity in chromatin regulation in yeast. While the epigenetic regulation of FLO10 and FLO11 expression appears similar and some key regulators (Sfl1) are shared, the requirement for chromatinmodifying proteins which underlie the silencing mechanism is quite different—Hda1 in the case of FLO11 and Hst1-Hst2 and Sir3 in the case of FLO10. This complexity probably foreshadows similar complexity in the regulation of other fungal adhesin families.
Key Concept Ranking
- Mitogen-Activated Protein Kinase Pathway
Domain structure of GPI-CWP adhesins. Four domains are shown, all required for function of the adhesins. SS indicates the signal sequence; GPI indicates the C-terminal sequence required for covalent attachment of the GPI anchor to the mature C terminus. The effector domain confers specificity of adherence. C-terminal to the effector domain, a region rich in Ser/Thr residues, which are glycosylated, acts as a spacer between the GPI anchor and the effector domain.
Chromosomal location of FLO genes in S. cerevisiae. Distances from the beginning of the telomeric repeats are indicated. Thick bars represent regions of homology between the FLO1, FLO5, and FLO9 loci.
Chromosomal location of EPA genes in strain BG2. Distances from the beginning of the telomeric repeats are indicated. Thick bars represent homology between different EPA loci: the EPA4 and EPA5 loci are essentially identical to each other across 7.6 kb, including the ORFs and the indicated 5and’ and 3’ intergenic regions. The EPA6 and EPA7 loci are highly homologous for the ORFs, for the 2.4 kb between the genes and the telomere, as well as for at least 4 kb upstream of the gene.
Silencing of the EPA1 to EPA7 loci. For the EPA1 to EPA7 loci, the genomic organization is shown. Below each gene is the transcriptional status of each gene grown under normal laboratory conditions. The triangles represent URA3 gene insertions made at each locus; below each insertion is the distance of the URA3 translational start from the telomeric repeats; above each triangle is the status of the correponding URA3 gene insertion in a wild-type cell, as measured by the ability to grow on 5-FOA plates. “off” means that the corresponding strain was 5-FOAr; “on” means that the corresponding strain was 5-FOAs. For the insertion between EPA1 and EPA2, “off / ” indicates that the strain yielded a small number of 5-FOAr colonies.
GPI-CWP with roles in adherence
Transcriptional regulators of FLO, ALS, and EPA genes