Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells

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作者
Peter J. Wen
Shona L. Osborne
Mark Zanin
Pei Ching Low
Hai-Tao A. Wang
Simone M. Schoenwaelder
Shaun P. Jackson
Roland Wedlich-Söldner
Bart Vanhaesebroeck
Damien J. Keating
Frédéric A. Meunier
机构
[1] The University of Queensland,Department of Human Physiology
[2] Queensland Brain Institute and School of Biomedical Sciences,undefined
[3] Flinders University,undefined
[4] Australian Centre for Blood Diseases,undefined
[5] Monash University,undefined
[6] Alfred Medical Research and Education Precinct,undefined
[7] Max Planck Institute of Biochemistry,undefined
[8] Research Group Cellular Dynamics and Cell Patterning,undefined
[9] Centre for Cell Signalling,undefined
[10] Barts Cancer Institute,undefined
[11] Queen Mary University of London,undefined
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Nature Communications | / 2卷
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摘要
Neurosecretory vesicles undergo docking and priming before Ca2+-dependent fusion with the plasma membrane. Although de novo synthesis of phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P2) is required for exocytosis, its precise contribution is still unclear. Here we show that inhibition of the p110δ isoform of PI3-kinase by IC87114 promotes a transient increase in PtdIns(4,5)P2, leading to a potentiation of exocytosis in chromaffin cells. We then exploit this pathway to examine the effect of a transient PtdIns(4,5)P2 increase on neurosecretory vesicles behaviour, outside the context of a secretagogue stimulation. Our results demonstrate that a rise in PtdIns(4,5)P2 is sufficient to promote the mobilization and recruitment of secretory vesicles to the plasma membrane via Cdc42-mediated actin reorganization. PtdIns(4,5)P2, therefore, orchestrates the actin-based conveyance of secretory vesicles to the plasma membrane.
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