N-acetylglucosamine-inducible CaGAP1 encodes a general amino acid permease which co-ordinates external nitrogen source response and morphogenesis in Candida albicans

Microbiology (Reading). 2003 Sep;149(Pt 9):2597-2608. doi: 10.1099/mic.0.26215-0.

Abstract

Candida albicans is able to grow in a variety of reversible morphological forms (yeast, pseudohyphal and hyphal) in response to various environmental signals, noteworthy among them being N-acetylglucosamine (GlcNAc). The gene CaGAP1, homologous to GAP1, which encodes the general amino acid permease from Saccharomyces cerevisiae, was isolated on the basis of its induction by GlcNAc through differential screening of a C. albicans genomic library. The gene could functionally complement an S. cerevisiae gap1 mutant by rendering it susceptible to the toxic amino acid analogue mimosine in minimal proline media. As in S. cerevisiae, mutation of the CaGAP1 gene had an effect on citrulline uptake in C. albicans. Northern analysis showed that GlcNAc-induced expression of CaGAP1 was further enhanced in synthetic minimal media supplemented with single amino acids (glutamate, proline and glutamine) or urea (without amino acids) but repressed in minimal ammonium media. Induction of CaGAP1 expression by GlcNAc was nullified in C. albicans deleted for the transcription factor CPH1 and the hyphal regulator RAS1, indicating the involvement of Cph1p-dependent Ras1p signalling in CaGAP1 expression. A homozygous mutant of this gene showed defective hyphal formation in solid hyphal-inducing media and exhibited less hyphal clumps when induced by GlcNAc. Alteration of morphology and short filamentation under nitrogen-starvation conditions in the heterozygous mutant suggested that CaGAP1 affects morphogenesis in a dose-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / pharmacology*
  • Amino Acid Transport Systems / genetics*
  • Amino Acid Transport Systems / metabolism
  • Amino Acids / metabolism
  • Base Sequence
  • Candida albicans / enzymology*
  • Candida albicans / genetics
  • Candida albicans / growth & development
  • DNA, Fungal / analysis
  • Gene Expression Regulation, Fungal / drug effects*
  • Molecular Sequence Data
  • Nitrogen / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism

Substances

  • Amino Acid Transport Systems
  • Amino Acids
  • DNA, Fungal
  • Nitrogen
  • Acetylglucosamine

Associated data

  • GENBANK/AF467941