期刊
NATURE
卷 499, 期 7457, 页码 233-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature12360
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资金
- Deutsche Forschungsgemeinschaft [SFB 740/C8, SFB 740/D7, SFB 958/A04, SFB 958/A07, SFB 958/Z02]
Phosphoinositides serve crucial roles in cell physiology, ranging from cell signalling to membrane traffic(1,2). Among the seven eukaryotic phosphoinositides the best studied species is phosphatidylinositol-4,5-bisphosphate (PI(4,5)P-2), which is concentrated at the plasma membrane where, among other functions, it is required for the nucleation of endocytic clathrin-coated pits(3-6). No phosphatidylinositol other than PI(4,5)P-2 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)(7). How phosphatidylinositol conversion from PI(4,5)P-2-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)P-2) by class II phosphatidylinositol-3-kinase C2 alpha (PI(3) K C2 alpha) spatiotemporally controls clathrin-mediated endocytosis. Depletion of PI(3,4)P-2 or PI(3)K C2 alpha impairs the maturation of late-stage clathrin-coated pits before fission. Timed formation of PI(3,4)P-2 by PI(3)K C2 alpha 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)P-2 in endocytosis and unravel a novel discrete function of PI(3,4)P-2 in a central cell physiological process.
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