A role in vacuolar arginine transport for yeast Btn1p and for human CLN3, the protein defective in Batten disease
A role in vacuolar arginine transport for yeast Btn1p and for human CLN3, the protein defective in Batten disease
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DOI：
10.1073/pnas.2136651100
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发表时间：
2003-12-23
影响因子：
11.1
通讯作者：
Pearce, DA
中科院分区：
文献类型：
--
作者：
Kim, Y;Ramirez-Montealegre, D;Pearce, DA
在酿酒酵母中，精氨酸进入液泡的运输先前已被证明是由一个假定的H+/精氨酸反向转运促进。我们证实，精氨酸运输到孤立的酵母液泡需要ATP，我们证明了一个功能性的液泡H+-ATP酶的要求。我们以前报道过，BTN 1（BTN 1-Delta），人类巴滕病基因CLN 3的直系同源物的缺失，导致在早期生长过程中液泡pH值下降。我们报告说，这种改变液泡pH值的btn 1-三角洲菌株的基础缺乏精氨酸运输到液泡，这导致内源性液泡精氨酸水平的耗尽。btnl-Delta中的这种精氨酸转运缺陷通过BTN 1或人CLN 3基因的表达来补充，并且强烈地提示了分别对于酵母Btn 1 p和人CLN 3蛋白，将碱性氨基酸转运或调节碱性氨基酸转运到液泡或溶酶体中的功能。我们认为，在溶酶体膜上的运输缺陷所造成的功能CLN 3的情况下，是主要的生化缺陷，导致巴滕病。
In Saccharomyces cerevisiae, transport of arginine into the vacuole has previously been shown to be facilitated by a putative H+/ arginine antiport. We confirm that transport of arginine into isolated yeast vacuoles requires ATP and we demonstrate a requirement for a functional vacuolar H+-ATPase. We previously reported that deletion of BTN1 (btn1-Delta), an ortholog of the human Batten disease gene CLN3, resulted in a decrease in vacuolar pH during early growth. We report that this altered vacuolar pH in btn1-Delta strains underlies a lack of arginine transport into the vacuole, which results in a depletion of endogenous vacuolar arginine levels. This arginine transport defect in btnl-Delta is complemented by expression of either BTN1 or the human CLN3 gene and strongly suggests a function for transport of, or regulation of the transport of, basic amino acids into the vacuole or lysosome for yeast Btn1p, and human CLN3 protein, respectively. We propose that defective transport at the lysosomal membrane caused by an absence of functional CLN3 is the primary biochemical defect that results in Batten disease.