The yeast model for Batten disease:: Mutations in btn1, btn2, and hsp30 alter pH homeostasis
The yeast model for Batten disease:: Mutations in btn1, btn2, and hsp30 alter pH homeostasis
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DOI：
10.1128/jb.182.22.6418-6423.2000
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发表时间：
2000-11-01
影响因子：
3.2
通讯作者：
Pearce, DA
中科院分区：
文献类型：
--
作者：
Chattopadhyay, S;Muzaffar, NE;Pearce, DA
酿酒酵母的BTN1基因产物与人类CLN3有39%的同源性和59%的相似性，CLN3与神经退行性疾病巴顿病有关。此外，BTN1-Delta菌株由于生长早期异常高的液泡酸度，质膜H+-ATPase活性升高。此前，DNA微阵列分析显示，BTN1-Delta菌株通过上调HSP30和BTN2两个基因的表达来补偿质膜H+-ATPase活性和液泡pH的变化。我们现在证明，在BTN1(+)或BTN1-Delta菌株中，HSP30或BTN2的缺失不会改变液泡pH，但确实会导致液泡H+-ATPase活性增加。BTN1、BTN2或HSP30的缺失不会改变细胞液的pH，但会降低pH的缓冲能力，并导致在含有山梨酸的低pH条件下生长不良，这种情况会导致细胞内pH动态平衡被破坏。Btn2p定位于胞浆，提示Btn2p在调节液泡和质膜H+-ATPase之间的pH动态平衡中起作用。在BTN1-Delta菌株中HSP30和BTN2的表达增加，而BTN1-Delta、hsp30-Delta和btn2-Delta菌株在低pH下的生长抑制，强化了我们的观点，即pH动态平衡改变是巴顿病的根本原因。
The BTN1 gene product of the yeast Saccharomyces cerevisiae is 39% identical and 59% similar to human CLN3, which is associated with the neurodegenerative disorder Batten disease. Furthermore, btn1-Delta strains have an elevated activity of the plasma membrane H+-ATPase due to an abnormally high vacuolar acidity during the early phase of growth. Previously, DNA microarray analysis revealed that btn1-Delta strains compensate for the altered plasma membrane H+-ATPase activity and vacuolar pH by elevating the expression of the two genes HSP30 and BTN2. We now show that deletion of either HSP30 or BTN2 in either BTN1(+) or btn1-Delta strains does not alter vacuolar pH but does lead to an increased activity of the vacuolar H+-ATPase. Deletion of BTN1, BTN2, or HSP30 does not alter cytosolic pH but diminishes pH buffering capacity and causes poor growth at low pH in a medium containing sorbic acid, a condition known to result in disturbed intracellular pH homeostasis. Btn2p was localized to the cytosol, suggesting a role in mediating pH homeostasis between the vacuole and plasma membrane H+-ATPase. Increased expression of HSP30 and BTN2 in btn1-Delta strains and diminished growth of btn1-Delta, hsp30-Delta, and btn2-Delta strains at low pH reinforce our view that altered pH homeostasis is the underlying cause of Batten disease.