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

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.

Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans

“…GAP1 was isolated in a screen to identify and characterize genes that could be involved in the regulation of morphogenesis and virulence induced by GlcNAc, an important hyphal induction regulator of C. albicans (35) (see below). A null mutant of GAP1 has a defect in filamentation under nitrogen starvation conditions, as well as upon the addition of GlcNAc (35). Addition of serum, however, still resulted in the induction of filamentation in the gap1 mutant, suggesting that Gap1 is not required for seruminduced hyphal formation.…”

Farnesol, a Morphogenetic Autoregulatory Substance in the Dimorphic Fungus Candida albicans, Inhibits Hyphae Growth through Suppression of a Mitogen-Activated Protein Kinase Cascade

“…18) To estimate whether farnesol inhibits MAP kinase cascade, we measured the expression of GAP1 in C. albicans treated with farnesol. The expression of GAP1 was suppressed by the farnesol (Fig.…”

Differential virulence of Candida albicansandC. dubliniensis: A role for Tor1 kinase?

“…of two permeases, the amino acid permease GAP1 16 and the ammonium permease MEP2, 17 which may act as sensors of nitrogen in the environment. Furthermore, in response to amino acid starvation, C. albicans activates the general amino acid control (GCN) response, which is activated by the transcription factor Gcn4.…”