磷酸肌醇是细胞内膜运输的重要调控因子。虽然“磷脂酰肌醇-4,5-二磷酸盐”的作用已被很好定性,但“磷脂酰肌醇-3,4-二磷酸盐” (PI(3,4)P2) 的作用仍不清楚。在这项研究中,Volker Haucke及其同事发现,PI(3,4)P2在名为Class II“磷脂酰肌醇-3-激酶C2C”(PI(3)K C2()的酶作用下的形成在时空上控制由“网格蛋白”介导的细胞内吞作用。这些发现提出了PI(3,4)P2在膜运输中的一个新颖功能。(生物谷Bioon.com)
生物谷推荐英文摘要:
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.