Publication Date:
2013-07-05
Description:
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 C2alpha (PI(3)K C2alpha) spatiotemporally controls clathrin-mediated endocytosis. Depletion of PI(3,4)P2 or PI(3)K C2alpha impairs the maturation of late-stage clathrin-coated pits before fission. Timed formation of PI(3,4)P2 by PI(3)K C2alpha 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Posor, York -- Eichhorn-Gruenig, Marielle -- Puchkov, Dmytro -- Schoneberg, Johannes -- Ullrich, Alexander -- Lampe, Andre -- Muller, Rainer -- Zarbakhsh, Sirus -- Gulluni, Federico -- Hirsch, Emilio -- Krauss, Michael -- Schultz, Carsten -- Schmoranzer, Jan -- Noe, Frank -- Haucke, Volker -- England -- Nature. 2013 Jul 11;499(7457):233-7. doi: 10.1038/nature12360. Epub 2013 Jul 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Leibniz Institut fur Molekulare Pharmakologie & Freie Universitat Berlin, Robert-Roessle-Strasse 10, 13125 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23823722" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
COS Cells
;
Cercopithecus aethiops
;
Class II Phosphatidylinositol 3-Kinases/metabolism
;
Clathrin-Coated Vesicles/metabolism
;
*Endocytosis
;
HEK293 Cells
;
HeLa Cells
;
Humans
;
Molecular Sequence Data
;
Phosphatidylinositol Phosphates/*metabolism
;
Phosphoric Monoester Hydrolases/metabolism
;
Sorting Nexins/metabolism
;
Time Factors
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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