Spatiotemporal control of endocytosis by phosphatidylinositol-3,4- bisphosphate

York Posor, Marielle Eichhorn-Gruenig, Dmytro Puchkov, Johannes Schöneberg, Alexander Ullrich, André Lampe, Rainer Müller, Sirus Zarbakhsh, Federico Gulluni, Emilio Hirsch, Michael Krauss, Carsten Schultz, Jan Schmoranzer, Frank Noé, Volker Haucke

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222 Scopus citations

Abstract

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)P 2), 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)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). 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 C2α (PI(3)K C2α) spatiotemporally controls clathrin-mediated endocytosis. Depletion of PI(3,4)P 2 or PI(3)K C2α impairs the maturation of late-stage clathrin-coated pits before fission. Timed formation of PI(3,4)P 2 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)P 2 in endocytosis and unravel a novel discrete function of PI(3,4)P 2 in a central cell physiological process.

Original languageEnglish (US)
Pages (from-to)233-237
Number of pages5
JournalNature
Volume499
Issue number7457
DOIs
StatePublished - Jul 5 2013

ASJC Scopus subject areas

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    Posor, Y., Eichhorn-Gruenig, M., Puchkov, D., Schöneberg, J., Ullrich, A., Lampe, A., Müller, R., Zarbakhsh, S., Gulluni, F., Hirsch, E., Krauss, M., Schultz, C., Schmoranzer, J., Noé, F., & Haucke, V. (2013). Spatiotemporal control of endocytosis by phosphatidylinositol-3,4- bisphosphate. Nature, 499(7457), 233-237. https://doi.org/10.1038/nature12360