The same receptor, G protein, and mitogen-activated protein kinase pathway activate different downstream regulators in the alternative white and opaque pheromone responses of Candida albicans

Mol Biol Cell. 2008 Mar;19(3):957-70. doi: 10.1091/mbc.e07-07-0688. Epub 2007 Dec 27.

Abstract

Candida albicans must undergo a switch from white to opaque to mate. Opaque cells then release mating type-specific pheromones that induce mating responses in opaque cells. Uniquely in C. albicans, the same pheromones induce mating-incompetent white cells to become cohesive, form an adhesive basal layer of cells on a surface, and then generate a thicker biofilm that, in vitro, facilitates mating between minority opaque cells. Through mutant analysis, it is demonstrated that the pathways regulating the white and opaque cell responses to the same pheromone share the same upstream components, including receptors, heterotrimeric G protein, and mitogen-activated protein kinase cascade, but they use different downstream transcription factors that regulate the expression of genes specific to the alternative responses. This configuration, although common in higher, multicellular systems, is not common in fungi, and it has not been reported in Saccharomyces cerevisiae. The implications in the evolution of multicellularity in higher eukaryotes are discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biofilms / drug effects
  • Biomarkers / metabolism
  • Candida albicans / cytology*
  • Candida albicans / enzymology*
  • Candida albicans / genetics
  • Candida albicans / physiology
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation, Fungal / drug effects
  • Genes, Switch
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Biological
  • Mutation / genetics
  • Phenotype
  • Pheromones / pharmacology*
  • Receptors, Pheromone / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Biomarkers
  • CPH1 protein, Candida albicans
  • Fungal Proteins
  • Pheromones
  • Receptors, Pheromone
  • Transcription Factors
  • Mitogen-Activated Protein Kinases
  • GTP-Binding Proteins