A Family of Yeast Proteins Mediating Bidirectional Vacuolar Amino Acid Transport

• Published in: The Journal of biological chemistry 2001-06, Vol.276 (26), p.23849-23857
• Main Authors: Russnak, Roland, Konczal, David, McIntire, Steven L.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; amino acid transporter; Amino Acids - metabolism; Aspartic Acid - metabolism; AVT1 protein; AVT3 protein; AVT4 protein; AVT6 protein; Biological Transport; Carrier Proteins - genetics; Carrier Proteins - physiology; Fluorescent Antibody Technique, Indirect; Fungal Proteins - genetics; Fungal Proteins - physiology; GABA Plasma Membrane Transport Proteins; gamma-Aminobutyric Acid - metabolism; Glutamic Acid - metabolism; Intracellular Membranes - metabolism; Membrane Proteins - genetics; Membrane Transport Proteins; Molecular Sequence Data; nigericin; Organic Anion Transporters; Phylogeny; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Sequence Homology, Amino Acid; Tyrosine - metabolism; Vacuoles - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M008028200

Seven genes in Saccharomyces cerevisiae are predicted to code for membrane-spanning proteins (designated AVT1–7) that are related to the neuronal γ-aminobutyric acid-glycine vesicular transporters. We have now demonstrated that four of these proteins mediate amino acid transport in vacuoles. One protein, AVT1, is required for the vacuolar uptake of large neutral amino acids including tyrosine, glutamine, asparagine, isoleucine, and leucine. Three proteins, AVT3, AVT4, and AVT6, are involved in amino acid efflux from the vacuole and, as such, are the first to be shown directly to transport compounds from the lumen of an acidic intracellular organelle. This function is consistent with the role of the vacuole in protein degradation, whereby accumulated amino acids are exported to the cytosol. Protein AVT6 is responsible for the efflux of aspartate and glutamate, an activity that would account for their exclusion from vacuoles in vivo. Transport by AVT1 and AVT6 requires ATP for function and is abolished in the presence of nigericin, indicating that the same pH gradient can drive amino acid transport in opposing directions. Efflux of tyrosine and other large neutral amino acids by the two closely related proteins, AVT3 and AVT4, is similar in terms of substrate specificity to transport systemh described in mammalian lysosomes and melanosomes. These findings suggest that yeast AVT transporter function has been conserved to control amino acid flux in vacuolar-like organelles.