The Candida albicans GAP Gene Family Encodes Permeases Involved in General and Specific Amino Acid Uptake and Sensing

Abstract

The Saccharomyces cerevisiae general amino acid permease Gap1 (ScGap1) not only mediates the uptake of most amino acids but also functions as a receptor for the activation of protein kinase A (PKA). Fungal pathogens can colonize different niches in the host, each containing various levels of different amino acids and sugars. The Candida albicans genome contains six genes homologous to the S. cerevisiae GAP1. The expression of these six genes in S. cerevisiae showed that the products of all six C. albicans genes differ in their transport capacities. C. albicans Gap2 (CaGap2) is the true orthologue of ScGap1 as it transports all tested amino acids. The other CaGap proteins have narrower substrate specificities though CaGap1 and CaGap6 transport several structurally unrelated amino acids. CaGap1, CaGap2, and CaGap6 also function as sensors. Upon detecting some amino acids, e.g., methionine, they are involved in a rapid activation of trehalase, a downstream target of PKA. Our data show that CaGAP genes can be functionally expressed in S. cerevisiae and that CaGap permeases communicate to the intracellular signal transduction pathway similarly to ScGap1.

New Insights into Sulfur Metabolism in Yeasts as Revealed by Studies of Yarrowia lipolytica

“…In Y. lipolytica, there are eight orthologs of the GAP1 gene, which encodes general amino acid transporters in S. cerevisiae. These genes could encode transporters with different specificities, as reported for Candida albicans by Kraidlova et al (24). Two of these genes were regulated under our conditions.…”

Gln3 is a main regulator of nitrogen assimilation in Candida glabrata

“…As we have shown, C. glabrata possesses orthologous genes to MEP2, GAP1 and GLN1. Orthologous genes to two of the three ammonium transporters (MEP1 and MEP2) and the general amino acid permease (GAP1) have also been found in C. albicans (Biswas & Morschh€ auser, 2005;Kraidlova et al, 2011). In addition, C. albicans possesses a putative GLN1 Fig.…”

Candida Survival Strategies

“…In addition to the reprogramming of metabolism in response to starvation, C. albicans possesses various transport mechanisms for peptides, amino acids, etc. that can be upregulated to acquire nutrients from degraded complex host molecules (Dunkel et al, 2013;Kraidlova, Van Zeebroeck, Van Dijck, & Sychrova, 2011;Ramachandra et al, 2014). The impact of metabolism upon Candida pathogenicity has recently been reviewed in detail (Brown, Budge, et al, 2014;Ene & Brown, 2014); thus we will only shortly summarize the current knowledge.…”