A family of yeast proteins mediating bidirectional vacuolar amino acid transport.
Seven genes in Saccharomyces cerevisiae are predicted to code for membrane-spanning proteins (designated AVT1-7) that are related to the neuronal gamma-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 system h 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.
Programs in Biological Science and Neuroscience, Gallo Center and Department of Neurology, University of California, San Francisco, UCSF School of Medicine, San Francisco, California 94143-0114, USA. russnak@itsa.ucsf.edu
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D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D019084:Fluorescent Antibody Technique, Indirect; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology*; D050485:GABA Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D027361:Organic Anion Transporters; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014443:Tyrosine / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D002352:Carrier Proteins; D005656:Fungal Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D029701:Saccharomyces cerevisiae Proteins; C513599:UGA4 protein, S cerevisiae; D001224:Aspartic Acid; D018698:Glutamic Acid; D014443:Tyrosine; D005680:gamma-Aminobutyric Acid