Assembly of a Fab1 Phosphoinositide Kinase Signaling Complex Requires the Fig4 Phosphoinositide Phosphatase
Assembly of a Fab1 Phosphoinositide Kinase Signaling Complex Requires the Fig4 Phosphoinositide Phosphatase
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DOI：
10.1091/mbc.e08-04-0405
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发表时间：
2008-10-01
影响因子：
3.3
通讯作者：
Emr, Scott D.
中科院分区：
文献类型：
--
作者：
Botelho, Roberto J.;Efe, Jem A.;Emr, Scott D.
磷脂酰肌醇-3，5-二磷酸[PtdIns（3，5）P-2]调节几种液泡功能，包括酸化、形态和膜运输。脂质激酶Fab 1将磷脂酰肌醇-3-磷酸[PtdIns（3）P]转化为PtdIns（3，5）P-2。PtdIns（3，5）P-2水平由接头样蛋白Vac 14和Fig 4 PtdIns（3，5）P-2特异性5-磷酸酶控制。有趣的是，Vac 14和Fig 4具有双重功能：它们都通过未知的机制参与PtdIns（3，5）P-2的合成和周转。我们现在表明，Fab 1，通过其伴侣蛋白样结构域，结合到Vac 14和图4，并形成一个液泡相关的信号复合物。Fab 1复合物通过Fab 1中的FYVE结构域与液泡上的PtdIns（3）P之间的相互作用被束缚到液泡。此外，Vac 14和Fig 4直接相互结合，并且相互依赖地与Fab 1激酶相互作用。我们的观察确定了一种蛋白质复合物，它将拮抗性Fab 1脂质激酶和Fig 4脂质磷酸酶整合到一个共同的功能单元中。我们提出了一个解释Vac 14和Fig 4在PtdIns（3，5）P-2的合成和周转中的双重作用的模型。
Phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P-2] regulates several vacuolar functions, including acidification, morphology, and membrane traffic. The lipid kinase Fab1 converts phosphatidylinositol-3-phosphate [PtdIns(3)P] to PtdIns(3,5)P-2. PtdIns(3,5)P-2 levels are controlled by the adaptor-like protein Vac14 and the Fig4 PtdIns(3,5)P-2-specific 5-phosphatase. Interestingly, Vac14 and Fig4 serve a dual function: they are both implicated in the synthesis and turnover of PtdIns(3,5)P-2 by an unknown mechanism. We now show that Fab1, through its chaperonin-like domain, binds to Vac14 and Fig4 and forms a vacuole-associated signaling complex. The Fab1 complex is tethered to the vacuole via an interaction between the FYVE domain in Fab1 and PtdIns(3)P on the vacuole. Moreover, Vac14 and Fig4 bind to each other directly and are mutually dependent for interaction with the Fab1 kinase. Our observations identify a protein complex that incorporates the antagonizing Fab1 lipid kinase and Fig4 lipid phosphatase into a common functional unit. We propose a model explaining the dual roles of Vac14 and Fig4 in the synthesis and turnover of PtdIns(3,5)P-2.