APSES proteins regulate morphogenesis and metabolism in Candida albicans

Thomas Doedt, Shankarling Krishnamurthy, Dirk P. Bockmuhl, Bernd Tebarth, Christian Stempel, Claire L. Russell, Alistair J. P. Brown, Joachim F. Ernst

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Abstract

Fungal APSES proteins regulate morphogenetic processes, including filamentation and differentiation. The human fungal pathogen Candida albicans contains two APSES proteins: the regulator Efg1p and its homologue Efh1p, described here. Overexpression of EFG1 or EFH1 led to similar phenotypes, including pseudohypha formation and opaque-white switching. An efh1 deletion generated no phenotype under most conditions but caused hyperfilamentation in an efg1 background under embedded or hypoxic conditions. This suggests cooperation of these APSES proteins in the suppression of an alternative morphogenetic signaling pathway. Genome-wide transcriptional profiling revealed that EFG1 and EFH1 regulate partially overlapping sets of genes associated with filament formation. Unexpectedly, Efg1p not only regulates genes involved in morphogenesis but also strongly influences the expression of metabolic genes, inducing glycolytic genes and repressing genes essential for oxidative metabolism. Using one- and two-hybrid assays, we further demonstrate that Efg1p is a repressor, whereas Efh1p is an activator of gene expression. Overall, the results suggest that Efh1p supports the regulatory functions of the primary regulator, Efg1p, and indicate a dual role for these APSES proteins in the regulation of fungal morphogenesis and metabolism.

Original languageEnglish
Pages (from-to)3167-3180
Number of pages14
JournalMolecular Biology of the Cell
Volume15
Issue number7
Early online date16 Apr 2004
DOIs
Publication statusPublished - 1 Jul 2004

Keywords

  • saccharomyces-cerevisiae
  • transcriptional regulators
  • filamentous growth
  • fungal development
  • gene
  • EFG1
  • yeast
  • sequence
  • construction
  • downstream

Cite this

Doedt, T., Krishnamurthy, S., Bockmuhl, D. P., Tebarth, B., Stempel, C., Russell, C. L., Brown, A. J. P., & Ernst, J. F. (2004). APSES proteins regulate morphogenesis and metabolism in Candida albicans. Molecular Biology of the Cell, 15(7), 3167-3180. https://doi.org/10.1091/mbc.E03-11-0782