Regulation of intracellular phosphatidylinositol-4-phosphate by the Sac1 lipid phosphatase
Regulation of intracellular phosphatidylinositol-4-phosphate by the Sac1 lipid phosphatase
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DOI：
10.1111/j.1600-0854.2004.00255.x
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发表时间：
2005-02-01
期刊：
影响因子：
4.5
通讯作者：
Mayinger, P
中科院分区：
文献类型：
--
作者：
Tahirovic, S;Schorr, M;Mayinger, P
磷脂酰肌醇4-磷酸（PtdIns（4）P）调节多种细胞过程，如肌动蛋白细胞骨架组织，高尔基体运输和液泡生物发生。PtdIns（4）P的合成和周转由一组特异性的脂质激酶和磷酸酶介导。在这里，我们表明，多磷酸肌醇磷酸酶Sac 1 p在PtdIns（4）P的隔室特异性调节中具有核心作用。我们发现，sac 1Delta突变体显示多效性，与液泡蛋白分选（Vps）所需的基因突变的合成致死相互作用。SAC 1基因的破坏也导致了晚期内吞途径的缺陷。这些运输表型与PtdIns（4）P在液泡膜上的大量积累相关。此外，sac 1突变体显示内质网PtdIns（4）P升高。PtdIns（4）P在内质网和空泡中的积累以及内吞缺陷可以通过PtdIns 4-激酶Stt 4p的突变来补偿。我们的研究结果表明，Sac 1 p的消除导致积累的Stt 4p-特异性PtdIns（4）P池在内膜损害后期内吞和空泡运输。我们的结论是Sac 1 p的功能限制PtdIns（4）P-依赖的过程，以特定的细胞内膜。
Phosphatidylinositol 4-phosphate (PtdIns(4)P) regulates diverse cellular processes, such as actin cytoskeletal organization, Golgi trafficking and vacuolar biogenesis. Synthesis and turnover of PtdIns(4)P is mediated by a set of specific lipid kinases and phosphatases. Here we show that the polyphosphoinositide phosphatase Sac1p has a central role in compartment-specific regulation of PtdIns(4)P. We have found that sac1Delta mutants show pleiotropic, synthetically lethal interactions with mutations in genes required for vacuolar protein sorting (Vps). Disruption of the SAC1 gene also caused a defect in the late endocytic pathway. These trafficking phenotypes correlated with a dramatic accumulation of PtdIns(4)P at vacuolar membranes. In addition, sac1 mutants displayed elevated endoplasmic reticulum PtdIns(4)P. The accumulation of PtdIns(4)P at the endoplasmic reticulum and vacuole and the endocytic defect could be compensated by mutations in the PtdIns 4-kinase Stt4p. Our results indicate that elimination of Sac1p causes accumulation of a Stt4p-specific PtdIns(4)P pool at internal membranes which impairs late endocytic and vacuolar trafficking. We conclude that Sac1p functions in confining PtdIns(4)P-dependent processes to specific intracellular membranes.