A family of yeast proteins mediating bidirectional vacuolar amino acid transport
A family of yeast proteins mediating bidirectional vacuolar amino acid transport
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DOI：
10.1074/jbc.m008028200
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发表时间：
2001-06-29
影响因子：
4.8
通讯作者：
McIntire, SL
中科院分区：
文献类型：
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作者：
Russnak, R;Konczal, D;McIntire, SL
酿酒酵母中的7个基因被预测编码跨膜蛋白(命名为AVT1-7)，这些蛋白与神经元的γ-氨基丁酸-甘氨酸囊泡转运蛋白相关。我们现在已经证明了这些蛋白质中的四种在液泡中介导氨基酸的运输，其中一种蛋白质AVT1是液泡摄取大的中性氨基酸所必需的，包括酪氨酸、谷氨酰胺、天冬氨酸、异亮氨酸和亮氨酸，三种蛋白质AVT3、AVT4和AVT6参与了氨基酸从液泡中的外流，因此，第一个被证明直接从酸性细胞内细胞器的管腔中运输化合物的蛋白质，这种功能与液泡在蛋白质降解中的作用是一致的，由此积累的氨基酸被输出到细胞质，蛋白质AVT6负责天冬氨酸和谷氨酸的外流。一种可以解释它们在体内被排除在液泡之外的活动。AVT1和AVT6的转运需要ATP来发挥作用，并且在黑素存在时被取消，这表明相同的pH梯度可以驱动氨基酸向相反的方向运输。在底物特异性方面，AVT3和AVT4这两种密切相关的蛋白质外流酪氨酸和其他大的中性氨基酸与哺乳动物溶酶体和黑素体中描述的运输系统h相似。这些发现表明，酵母AVT转运蛋白的功能是保守的，可以控制液泡状细胞器中的氨基酸流动。
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.