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

Abstract

Candida albicansis able to grow in a variety of reversible morphological forms (yeast, pseudohyphal and hyphal) in response to various environmental signals, noteworthy among them beingN-acetylglucosamine (GlcNAc). The geneCaGAP1, homologous toGAP1, which encodes the general amino acid permease fromSaccharomyces cerevisiae, was isolated on the basis of its induction by GlcNAc through differential screening of aC. albicansgenomic library. The gene could functionally complement anS. cerevisiae gap1mutant by rendering it susceptible to the toxic amino acid analogue mimosine in minimal proline media. As inS. cerevisiae, mutation of theCaGAP1gene had an effect on citrulline uptake inC. albicans. Northern analysis showed that GlcNAc-induced expression ofCaGAP1was 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 ofCaGAP1expression by GlcNAc was nullified inC. albicansdeleted for the transcription factorCPH1and the hyphal regulatorRAS1, indicating the involvement of Cph1p-dependent Ras1p signalling inCaGAP1expression. 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 thatCaGAP1affects morphogenesis in a dose-dependent manner.