BTN1, the Saccharomyces cerevisiae homolog to the human Batten disease gene, is involved in phospholipid distribution
BTN1, the Saccharomyces cerevisiae homolog to the human Batten disease gene, is involved in phospholipid distribution
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DOI：
10.1242/dmm.008490
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发表时间：
2012-03-01
影响因子：
4.3
通讯作者：
Pearce, David A.
中科院分区：
文献类型：
--
作者：
Padilla-Lopez, Sergio;Langager, Deanna;Pearce, David A.
BTN 1是人CLN 3（在Batten病中有缺陷）的酵母同源物，可能通过调节液泡型H+-ATP酶（V-ATP酶）活性参与液泡pH的调节。然而，我们报告说，Btn 1 p和V-ATPase复合物不物理相互作用，这表明Btn 1 p对V-ATPase的任何影响都是间接的。由于膜脂环境在膜蛋白的活性和功能中起着至关重要的作用，我们研究了缺乏BTN 1的细胞是否改变了膜磷脂含量。BTN 1（btn 1-Delta）的缺失导致线粒体和液泡膜中磷脂酰乙醇胺（PtdEtn）水平的降低。在酵母中存在两种磷脂酰丝氨酸（PtdSer）脱羧酶，Psd 1 p和Psd 2 p，并且这两种蛋白质分别负责线粒体和高尔基体内体中PtdEtn的合成。BTN 1和PSD 1（btn 1-Delta psd 1-Delta）的缺失导致与线粒体（MAMs）相关的ER膜中PtdEtn水平进一步降低，PtdSer水平平行增加。荧光标记的PtdSer（NBD-PtdSer）转运试验表明，在btn 1-Delta细胞中，NBD-PtdSer从ER向线粒体和内体和/或液泡的转运受到影响。此外，btn 1-Delta通过肯尼迪途径影响PtdEtn的合成，并削弱psd 1-Delta细胞通过添加乙醇胺将线粒体和液泡中PtdEtn恢复到正常水平的能力。总之，缺乏Btn 1 p改变磷脂水平，并可能在调节其亚细胞分布中发挥作用。
BTN1, the yeast homolog to human CLN3 (which is defective in Batten disease), has been implicated in the regulation of vacuolar pH, potentially by modulating vacuolar-type H+-ATPase (V-ATPase) activity. However, we report that Btn1p and the V-ATPase complex do not physically interact, suggesting that any influence that Btn1p has on V-ATPase is indirect. Because membrane lipid environment plays a crucial role in the activity and function of membrane proteins, we investigated whether cells lacking BTN1 have altered membrane phospholipid content. Deletion of BTN1 (btn1-Delta) led to a decreased level of phosphatidylethanolamine (PtdEtn) in both mitochondrial and vacuolar membranes. In yeast there are two phosphatidylserine (PtdSer) decarboxylases, Psd1p and Psd2p, and these proteins are responsible for the synthesis of PtdEtn in mitochondria and Golgi-endosome, respectively. Deletion of both BTN1 and PSD1 (btn1-Delta psd1-Delta) led to a further decrease in levels of PtdEtn in ER membranes associated to mitochondria (MAMs), with a parallel increase in PtdSer. Fluorescent-labeled PtdSer (NBD-PtdSer) transport assays demonstrated that transport of NBD-PtdSer from the ER to both mitochondria and endosomes and/or vacuole is affected in btn1-Delta cells. Moreover, btn1-Delta affects the synthesis of PtdEtn by the Kennedy pathway and impairs the ability of psd1-Delta cells to restore PtdEtn to normal levels in mitochondria and vacuoles by ethanolamine addition. In summary, lack of Btn1p alters phospholipid levels and might play a role in regulating their subcellular distribution.