The Yak1 kinase is involved in the initiation and maintenance of hyphal growth in Candida albicans

Mol Biol Cell. 2008 May;19(5):2251-66. doi: 10.1091/mbc.e07-09-0960. Epub 2008 Mar 5.

Abstract

Members of the dual-specificity tyrosine-phosphorylated and regulated kinase (DYRK) family perform a variety of functions in eukaryotes. We used gene disruption, targeted pharmacologic inhibition, and genome-wide transcriptional profiling to dissect the function of the Yak1 DYRK in the human fungal pathogen Candida albicans. C. albicans strains with mutant yak1 alleles showed defects in the yeast-to-hypha transition and in maintaining hyphal growth. They also could not form biofilms. Despite their in vitro filamentation defect, C. albicans yak1Delta/yak1Delta mutants remained virulent in animal models of systemic and oropharyngeal candidiasis. Transcriptional profiling showed that Yak1 was necessary for the up-regulation of only a subset of hypha-induced genes. Although downstream targets of the Tec1 and Bcr1 transcription factors were down-regulated in the yak1Delta/yak1Delta mutant, TEC1 and BCR1 were not. Furthermore, 63% of Yak1-dependent, hypha-specific genes have been reported to be negatively regulated by the transcriptional repressor Tup1 and inactivation of TUP1 in the yak1Delta/yak1Delta mutant restored filamentation, suggesting that Yak1 may function upstream of Tup1 in governing hyphal emergence and maintenance.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • Base Sequence
  • Biofilms / drug effects
  • Candida albicans / enzymology*
  • Candida albicans / growth & development
  • Candida albicans / pathogenicity
  • Candida albicans / ultrastructure
  • Cell Differentiation / drug effects
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Deletion
  • Gene Expression Regulation, Fungal / drug effects
  • Genes, Fungal
  • Hyphae / cytology
  • Hyphae / enzymology*
  • Hyphae / growth & development*
  • Hyphae / ultrastructure
  • Mice
  • Molecular Sequence Data
  • Pyrazoles / pharmacology
  • Pyrimidines / pharmacology
  • Up-Regulation / drug effects
  • Virulence / drug effects

Substances

  • 4-amino-1-tert-butyl-3-(1'-naphthylmethyl)pyrazolo(3,4-d)pyrimidine
  • Fungal Proteins
  • Pyrazoles
  • Pyrimidines
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases