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

Research output: Contribution to journalArticle

196 Citations (Scopus)

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 - 2013
Externally publishedYes

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Phosphatidylinositols
Endocytosis
Clathrin
Cell Physiological Phenomena
Class II Phosphatidylinositol 3-Kinases
Endosomes
Cell Membrane
phosphatidylinositol 3,4-diphosphate
Membranes
phosphatidylinositol 3-phosphate

ASJC Scopus subject areas

  • General

Cite this

Posor, Y., Eichhorn-Gruenig, M., Puchkov, D., Schöneberg, J., Ullrich, A., Lampe, A., ... Haucke, V. (2013). Spatiotemporal control of endocytosis by phosphatidylinositol-3,4- bisphosphate. Nature, 499(7457), 233-237. https://doi.org/10.1038/nature12360

Spatiotemporal control of endocytosis by phosphatidylinositol-3,4- bisphosphate. / Posor, York; Eichhorn-Gruenig, Marielle; Puchkov, Dmytro; Schöneberg, Johannes; Ullrich, Alexander; Lampe, André; Müller, Rainer; Zarbakhsh, Sirus; Gulluni, Federico; Hirsch, Emilio; Krauss, Michael; Schultz, Carsten; Schmoranzer, Jan; Noé, Frank; Haucke, Volker.

In: Nature, Vol. 499, No. 7457, 2013, p. 233-237.

Research output: Contribution to journalArticle

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, vol. 499, no. 7457, pp. 233-237. https://doi.org/10.1038/nature12360
Posor Y, Eichhorn-Gruenig M, Puchkov D, Schöneberg J, Ullrich A, Lampe A et al. Spatiotemporal control of endocytosis by phosphatidylinositol-3,4- bisphosphate. Nature. 2013;499(7457):233-237. https://doi.org/10.1038/nature12360
Posor, York ; Eichhorn-Gruenig, Marielle ; Puchkov, Dmytro ; Schöneberg, Johannes ; Ullrich, Alexander ; Lampe, André ; Müller, Rainer ; Zarbakhsh, Sirus ; Gulluni, Federico ; Hirsch, Emilio ; Krauss, Michael ; Schultz, Carsten ; Schmoranzer, Jan ; Noé, Frank ; Haucke, Volker. / Spatiotemporal control of endocytosis by phosphatidylinositol-3,4- bisphosphate. In: Nature. 2013 ; Vol. 499, No. 7457. pp. 233-237.
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