TY - JOUR
T1 - Spatiotemporal control of endocytosis by phosphatidylinositol-3,4- bisphosphate
AU - Posor, York
AU - Eichhorn-Gruenig, Marielle
AU - Puchkov, Dmytro
AU - Schöneberg, Johannes
AU - Ullrich, Alexander
AU - Lampe, André
AU - Müller, Rainer
AU - Zarbakhsh, Sirus
AU - Gulluni, Federico
AU - Hirsch, Emilio
AU - Krauss, Michael
AU - Schultz, Carsten
AU - Schmoranzer, Jan
AU - Noé, Frank
AU - Haucke, Volker
N1 - Funding Information:
Acknowledgements We thank E. Ungewickell, P. Di Fiore, P. De Camilli, H. McMahon, E. Wancker, T. Südhof and S. Carlsson for antibodies, L. Cantley, T. Takenawa, M. Wymann, T. Ross, O. Daumke and W. Yang for plasmids, and O. Daumke, B. Eickolt and F. Wieland for critical comments. Supported by grants from the Deutsche Forschungsgemeinschaft (SFB 740/C8; SFB 740/D7; SFB 958/A04; SFB 958/A07; SFB 958/Z02).
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84880507763&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880507763&partnerID=8YFLogxK
U2 - 10.1038/nature12360
DO - 10.1038/nature12360
M3 - Article
C2 - 23823722
AN - SCOPUS:84880507763
SN - 0028-0836
VL - 499
SP - 233
EP - 237
JO - Nature
JF - Nature
IS - 7457
ER -