The Vac14p-Fig4p complex acts independently of Vac7p and couples PI3,5P2 synthesis and turnover.

The Vac14p-Fig4p complex acts independently of Vac7p and couples PI3,5P2 synthesis and turnover.
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DOI:
10.1083/jcb.200512105
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发表时间:
2006-02-27
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Weisman LS
Weisman LS
中科院分区:
其他
文献类型:
--
作者:
Duex JE;Tang F;Weisman LS

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磷酸肌醇信号脂质在多种细胞途径中发挥作用。这些信号脂质水平的动态变化调节多个过程。特别是,当酿酒酵母细胞暴露于高渗休克时,PI3,5P2(磷脂酰肌醇 [PI]3,5-二磷酸)水平短暂增加 20 倍。这导致液泡经历多次急性变化。 PI3、5P2 水平的控制是通过调节其合成和周转来实现的。合成由 PI3P 5-激酶 Fab1p 催化,周转由 PI3,5P2 5-磷酸酶 Fig4p 催化。在这项研究中,我们证明了两种假定的 Fab1p 激活剂 Vac7p 和 Vac14p 独立调节 Fab1p 活性。虽然Vac7p仅调节Fab1p,但令人惊讶的是,我们发现Vac14同时调节Fab1p和Fig4p。此外,Fig4p 本身在 PI3、5P2 合成和周转中发挥作用。在 Vac7p 不存在和存在的情况下,Vac14p-Fig4p 复合物控制着高渗休克引起的 PI3,5P2 水平的增加。这些发现表明 PI3、5P2 的动态变化是通过合成和周转的紧密耦合来控制的。
Phosphoinositide-signaling lipids function in diverse cellular pathways. Dynamic changes in the levels of these signaling lipids regulate multiple processes. In particular, when Saccharomyces cerevisiae cells are exposed to hyperosmotic shock, PI3,5P2 (phosphatidylinositol [PI] 3,5-bisphosphate) levels transiently increase 20-fold. This causes the vacuole to undergo multiple acute changes. Control of PI3,5P2 levels occurs through regulation of both its synthesis and turnover. Synthesis is catalyzed by the PI3P 5-kinase Fab1p, and turnover is catalyzed by the PI3,5P2 5-phosphatase Fig4p. In this study, we show that two putative Fab1p activators, Vac7p and Vac14p, independently regulate Fab1p activity. Although Vac7p only regulates Fab1p, surprisingly, we find that Vac14 regulates both Fab1p and Fig4p. Moreover, Fig4p itself functions in both PI3,5P2 synthesis and turnover. In both the absence and presence of Vac7p, the Vac14p–Fig4p complex controls the hyperosmotic shock–induced increase in PI3,5P2 levels. These findings suggest that the dynamic changes in PI3,5P2 are controlled through a tight coupling of synthesis and turnover.
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