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.

Department of Membrane Transport Institute of Physiology AS CR Videnska 1083 142 20 Prague 4 Czech Republic

Zobrazit více v PubMed

Alvarez F. J., Konopka J. B. 2007. Identification of an N-acetylglucosamine transporter that mediates hyphal induction in Candida albicans. Mol. Biol. Cell 18:965–975 PubMed PMC

Andre B. 1995. An overview of membrane transport proteins in Saccharomyces cerevisiae. Yeast 11:1575–1611 PubMed

Arnaud M. B., et al. 2007. Sequence resources at the Candida Genome Database. Nucleic Acids Res. 35:D452–456 PubMed PMC

Biswas S., Roy M., Datta A. 2003. N-acetylglucosamine-inducible CaGAP1 encodes a general amino acid permease which co-ordinates external nitrogen source response and morphogenesis in Candida albicans. Microbiology 149:2597–2608 PubMed

Biswas S., Van Dijck P., Datta A. 2007. Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans. Microbiol. Mol. Biol. Rev. 71:348–376 PubMed PMC

Bonini B. M., Van Dijck P., Thevelein J. M. 2003. Uncoupling of the glucose growth defect and the deregulation of glycolysis in Saccharomyces cerevisiae Tps1 mutants expressing trehalose-6-phosphate-insensitive hexokinase from Schizosaccharomyces pombe. Biochim. Biophys. Acta 1606:83–93 PubMed

Bradford M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:248–254 PubMed

Brega E., Zufferey R., Mamoun C. B. 2004. Candida albicans Csy1p is a nutrient sensor important for activation of amino acid uptake and hyphal morphogenesis. Eukaryot. Cell 3:135–143 PubMed PMC

Cannon R. D., et al. 2009. Efflux-mediated antifungal drug resistance. Clin. Microbiol. Rev. 22:291–321 PubMed PMC

Chen E. J., Kaiser C. A. 2002. Amino acids regulate the intracellular trafficking of the general amino acid permease of Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U. S. A. 99:14837–14842 PubMed PMC

Cherry J. M., et al. 1997. Genetic and physical maps of Saccharomyces cerevisiae. Nature 387:67–73 PubMed PMC

De Boer M., et al. 1998. Regulation of expression of the amino acid transporter gene BAP3 in Saccharomyces cerevisiae. Mol. Microbiol. 30:603–613 PubMed

De Rosa F. G., Garazzino S., Pasero D., Di Perri G., Ranieri V. M. 2009. Invasive candidiasis and candidemia: new guidelines. Minerva Anestesiol. 75:453–458 PubMed

Didion T., Grauslund M., Kielland-Brandt M. C., Andersen H. A. 1996. Amino acids induce expression of BAP2, a branched-chain amino acid permease gene in Saccharomyces cerevisiae. J. Bacteriol. 178:2025–2029 PubMed PMC

Donaton M. C., et al. 2003. The Gap1 general amino acid permease acts as an amino acid sensor for activation of protein kinase A targets in the yeast Saccharomyces cerevisiae. Mol. Microbiol. 50:911–929 PubMed

During-Olsen L., Regenberg B., Gjermansen C., Kielland-Brandt M. C., Hansen J. 1999. Cysteine uptake by Saccharomyces cerevisiae is accomplished by multiple permeases. Curr. Genet. 35:609–617 PubMed

Gilstring C. F., Ljungdahl P. O. 2000. A method for determining the in vivo topology of yeast polytopic membrane proteins demonstrates that Gap1p fully integrates into the membrane independently of Shr3p. J. Biol. Chem. 275:31488–31495 PubMed

Grenson M., Hou C., Crabeel M. 1970. Multiplicity of the amino acid permeases in Saccharomyces cerevisiae. IV. Evidence for a general amino acid permease. J. Bacteriol. 103:770–777 PubMed PMC

Hall R. A., Muhlschlegel F. A. 2010. A multi-protein complex controls cAMP signalling and filamentation in the fungal pathogen Candida albicans. Mol. Microbiol. 75:534–537 PubMed

Harcus D., Nantel A., Marcil A., Rigby T., Whiteway M. 2004. Transcription profiling of cyclic AMP signaling in Candida albicans. Mol. Biol. Cell 15:4490–4499 PubMed PMC

Helliwell S. B., Losko S., Kaiser C. A. 2001. Components of a ubiquitin ligase complex specify polyubiquitination and intracellular trafficking of the general amino acid permease. J. Cell Biol. 153:649–662 PubMed PMC

Hill J. E., Myers A. M., Koerner T. J., Tzagoloff A. 1986. Yeast/E. coli shuttle vectors with multiple unique restriction sites. Yeast 2:163–167 PubMed

Hoffman C. S., Winston F. 1987. A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene 57:267–272 PubMed

Hogan D. A., Sundstrom P. 2009. The Ras/cAMP/PKA signaling pathway and virulence in Candida albicans. Future Microbiol. 4:1263–1270 PubMed

Horak J. 1997. Yeast nutrient transporters. Biochim. Biophys. Acta 1331:41–79 PubMed

Reference deleted.

Hruskova-Heidingsfeldova O. 2008. Secreted proteins of Candida albicans. Front. Biosci. 13:7227–7242 PubMed

Jauniaux J. C., Grenson M. 1990. GAP1, the general amino acid permease gene of Saccharomyces cerevisiae. Nucleotide sequence, protein similarity with the other bakers yeast amino acid permeases, and nitrogen catabolite repression. Eur. J. Biochem. 190:39–44 PubMed

Reference deleted.

Jones T., et al. 2004. The diploid genome sequence of Candida albicans. Proc. Natl. Acad. Sci. U. S. A. 101:7329–7334 PubMed PMC

Kinclova O., Ramos J., Potier S., Sychrova H. 2001. Functional study of the Saccharomyces cerevisiae Nha1p C-terminus. Mol. Microbiol. 40:656–668 PubMed

Kinclova-Zimmermannova O., Sychrova H. 2007. Plasma-membrane Cnh1 Na+/H+ antiporter regulates potassium homeostasis in Candida albicans. Microbiology 153:2603–2612 PubMed

Kota J., Gilstring C. F., Ljungdahl P. O. 2007. Membrane chaperone Shr3 assists in folding amino acid permeases preventing precocious ERAD. J. Cell Biol. 176:617–628 PubMed PMC

Lee K. L., Buckley H. R., Campbell C. C. 1975. An amino acid liquid synthetic medium for the development of mycelial and yeast forms of Candida albicans. Sabouraudia 13:148–153 PubMed

Liao W. L., Ramon A. M., Fonzi W. A. 2008. GLN3 encodes a global regulator of nitrogen metabolism and virulence of C. albicans. Fungal Genet. Biol. 45:514–526 PubMed PMC

Ljungdahl P. O. 2009. Amino-acid-induced signalling via the SPS-sensing pathway in yeast. Biochem. Soc. Trans. 37:242–247 PubMed

Ljungdahl P. O., Gimeno C. J., Styles C. A., Fink G. R. 1992. SHR3: a novel component of the secretory pathway specifically required for localization of amino acid permeases in yeast. Cell 71:463–478 PubMed

Lowry O. H., Rosebrough N. J., Farr A. L., Randall R. J. 1951. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193:265–275 PubMed

Martinez P., Ljungdahl P. O. 2004. An ER packaging chaperone determines the amino acid uptake capacity and virulence of Candida albicans. Mol. Microbiol. 51:371–384 PubMed

Matejckova A., Sychrova H. 1996. Properties of Candida albicans CAN1 permease expressed in Saccharomyces cerevisiae. Folia Microbiol. 41:107–109 PubMed

Naglik J., Albrecht A., Bader O., Hube B. 2004. Candida albicans proteinases and host/pathogen interactions. Cell Microbiol. 6:915–926 PubMed

Naglik J. R., Challacombe S. J., Hube B. 2003. Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiol. Mol. Biol. Rev. 67:400–428 PubMed PMC

Noble S. M., Johnson A. D. 2007. Genetics of Candida albicans, a diploid human fungal pathogen. Annu. Rev. Genet. 41:193–211 PubMed

Ohama T., et al. 1993. Non-universal decoding of the leucine codon CUG in several Candida species. Nucleic Acids Res. 21:4039–4045 PubMed PMC

Pernambuco M. B., et al. 1996. Glucose-triggered signalling in Saccharomyces cerevisiae: different requirements for sugar phosphorylation between cells grown on glucose and those grown on non-fermentable carbon sources. Microbiology 142:1775–1782 PubMed

Regenberg B., Kielland-Brandt M. C. 2001. Amino acid residues important for substrate specificity of the amino acid permeases Can1p and Gnp1p in Saccharomyces cerevisiae. Yeast 18:1429–1440 PubMed

Rossignol T., et al. 2008. CandidaDB: a multi-genome database for Candida species and related Saccharomycotina. Nucleic Acids Res. 36:D557–D561 PubMed PMC

Rupp S. 2004. Proteomics on its way to study host-pathogen interaction in Candida albicans. Curr. Opin. Microbiol. 7:330–335 PubMed

Rupp S., Summers E., Lo H. J., Madhani H., Fink G. 1999. MAP kinase and cAMP filamentation signaling pathways converge on the unusually large promoter of the yeast FLO11 gene. EMBO J. 18:1257–1269 PubMed PMC

Saitou N., Nei M. 1987. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4:406–425 PubMed

Shukla S., et al. 2003. Functional characterization of Candida albicans ABC transporter Cdr1p. Eukaryot. Cell 2:1361–1375 PubMed PMC

Soetens O., De Craene J. O., Andre B. 2001. Ubiquitin is required for sorting to the vacuole of the yeast general amino acid permease, Gap1. J. Biol. Chem. 276:43949–43957 PubMed

Sophianopoulou V., Diallinas G. 1995. Amino acid transporters of lower eukaryotes: regulation, structure and topogenesis. FEMS Microbiol. Rev. 16:53–75 PubMed

Stanbrough M., Magasanik B. 1995. Transcriptional and posttranslational regulation of the general amino acid permease of Saccharomyces cerevisiae. J. Bacteriol. 177:94–102 PubMed PMC

Sychrova H., Chevallier M. R. 1993. Cloning and sequencing of the Saccharomyces cerevisiae gene LYP1 coding for a lysine-specific permease. Yeast 9:771–782 PubMed

Thevelein J. M. 1994. Signal transduction in yeast. Yeast 10:1753–1790 PubMed

Tullin S., Gjermansen C., Kielland-Brandt M. C. 1991. A high-affinity uptake system for branched-chain amino acids in Saccharomyces cerevisiae. Yeast 7:933–941 PubMed

van Dyk D., Pretorius I. S., Bauer F. F. 2005. Mss11p is a central element of the regulatory network that controls FLO11 expression and invasive growth in Saccharomyces cerevisiae. Genetics 169:91–106 PubMed PMC

Van Zeebroeck G., Bonini B. M., Versele M., Thevelein J. M. 2009. Transport and signaling via the amino acid binding site of the yeast Gap1 amino acid transceptor. Nat. Chem. Biol. 5:45–52 PubMed

Zaman S., Lippman S. I., Zhao X., Broach J. R. 2008. How Saccharomyces responds to nutrients. Annu. Rev. Genet. 42:27–81 PubMed

Zeng Y. B., Qian Y. S., Ma L., Gu H. N. 2007. Genome-wide expression profiling of the response to terbinafine in Candida albicans using a cDNA microarray analysis. Chin Med. J. 120:807–813 PubMed

Characterization of the Candida albicans Amino Acid Permease Family: Gap2 Is the Only General Amino Acid Permease and Gap4 Is an S-Adenosylmethionine (SAM) Transporter Required for SAM-Induced Morphogenesis