Metabolically Stabilized Derivatives of Phosphatidylinositol 4-Phosphate: Synthesis and Applications
Metabolically Stabilized Derivatives of Phosphatidylinositol 4-Phosphate: Synthesis and Applications
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DOI：
10.1016/j.chembiol.2011.07.022
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发表时间：
2011-10-28
影响因子：
--
通讯作者：
Kutateladze, Tatiana G.
中科院分区：
文献类型：
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作者：
He, Ju;Gajewiak, Joanna;Kutateladze, Tatiana G.
磷脂酰肌醇4-磷酸(PtdIns(4)P)脂是真核膜的重要组成部分，也是高尔基复合体的标志物。在这里，我们开发了代谢稳定的(MS)类似物PtdIns(4)P和1，4-二磷酸肌醇(IP(2))头基衍生物，并证明这些化合物可以完全替代天然脂类，保持其生理活性。PtdIns(4)P的亚甲基磷酸盐(MP)和硫代磷酸(PT)类似物以及氨基己基(AH)-1P(2)探针被四个磷酸适配蛋白1(FAPP1)的PtdIns(4)P特异性PH结构域识别。FAPP1与PtdIns(4)P衍生物的结合刺激PH结构域插入到脂质层中，并诱导膜管状。MS类似物和IP(2)探针对于识别蛋白质效应器和表征跨高尔基体网络(TGN)中依赖P的PtdIns(4)信号级联可能是非常有价值的。
Phosphatidylinositol 4-phosphate (PtdIns(4)P) lipid is an essential component of eukaryotic membranes and a marker of the Golgi complex. Here, we developed metabolically stabilized (ms) analogs of PtdIns(4)P and the inositol 1,4-bisphosphate (IP(2)) head group derivative and demonstrated that these compounds can substitute the natural lipid fully retaining its physiological activities. The methylenephosphonate (MP) and phosphorothioate (PT) analogs of PtdIns(4)P and the aminohexyl (AH)-1P(2) probe are recognized by the PtdIns(4)P-specific PH domain of four phosphate adaptor protein 1 (FAPP1). Binding of FAPP1 to the PtdIns(4)P derivatives stimulates insertion of the PH domain into the lipid layers and induces tubulation of membranes. Both ms analogs and IP(2) probes could be invaluable for identifying protein effectors and characterizing PtdIns(4)P-dependent signaling cascades within the trans-Golgi network (TGN).