磷酸肌醇是細(xì)胞內(nèi)膜運(yùn)輸?shù)闹匾{(diào)控因子,。雖然“磷脂酰肌醇-4,5-二磷酸鹽”的作用已被很好定性,,但“磷脂酰肌醇-3,4-二磷酸鹽” (PI(3,4)P2) 的作用仍不清楚。在這項(xiàng)研究中,,Volker Haucke及其同事發(fā)現(xiàn),,PI(3,4)P2在名為Class II“磷脂酰肌醇-3-激酶C2C”(PI(3)K C2()的酶作用下的形成在時(shí)空上控制由“網(wǎng)格蛋白”介導(dǎo)的細(xì)胞內(nèi)吞作用。這些發(fā)現(xiàn)提出了PI(3,4)P2在膜運(yùn)輸中的一個(gè)新穎功能,。(生物谷Bioon.com)
生物谷推薦英文摘要:
Nature doi: 10.1038/nature12360
Spatiotemporal control of endocytosis by phosphatidylinositol-3,4-bisphosphate
York Posor, Marielle Eichhorn-Gruenig, Dmytro Puchkov, Johannes Sch?neberg, Alexander Ullrich, André Lampe, Rainer Müller, Sirus Zarbakhsh, Federico Gulluni, Emilio Hirsch, Michael Krauss, Carsten Schultz, Jan Schmoranzer, Frank Noé & Volker Haucke
Phosphoinositides serve crucial roles in cell physiology, ranging from cell signalling to membrane traffic. Among the seven eukaryotic phosphoinositides the best studied species is phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), which is concentrated at the plasma membrane where, among other functions, it is required for the nucleation of endocytic clathrin-coated pits. No phosphatidylinositol other than PI(4,5)P2 has been implicated in clathrin-mediated endocytosis, whereas the subsequent endosomal stages of the endocytic pathway are dominated by phosphatidylinositol-3-phosphates(PI(3)P). How phosphatidylinositol conversion from PI(4,5)P2-positive endocytic intermediates to PI(3)P-containing endosomes is achieved is unclear. Here we show that formation of phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2) by class II phosphatidylinositol-3-kinase C2α (PI(3)K C2α) spatiotemporally controls clathrin-mediated endocytosis. Depletion of PI(3,4)P2 or PI(3)K C2α impairs the maturation of late-stage clathrin-coated pits before fission. Timed formation of PI(3,4)P2 by PI(3)K C2α is required for selective enrichment of the BAR domain protein SNX9 at late-stage endocytic intermediates. These findings provide a mechanistic framework for the role of PI(3,4)P2 in endocytosis and unravel a novel discrete function of PI(3,4)P2 in a central cell physiological process.