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

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Abstract
The Saccharomyces cerevisiae general amino acid permease Gap1 ( Sc Gap1) 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 ( Ca Gap2) is the true orthologue of Sc Gap1 as it transports all tested amino acids. The other Ca Gap proteins have narrower substrate specificities though Ca Gap1 and Ca Gap6 transport several structurally unrelated amino acids. Ca Gap1, Ca Gap2, and Ca Gap6 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 Ca Gap permeases communicate to the intracellular signal transduction pathway similarly to Sc Gap1.

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