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

• Published in: Nature communications 2011-10, Vol.2 (1), p.491-491, Article 491
• Main Authors: Wen, Peter J., Osborne, Shona L., Zanin, Mark, Low, Pei Ching, Wang, Hai-Tao A., Schoenwaelder, Simone M., Jackson, Shaun P., Wedlich-Söldner, Roland, Vanhaesebroeck, Bart, Keating, Damien J., Meunier, Frédéric A.
• Format: Article
• Language: English
• Subjects: 631/378/548/2589; 631/443/319/367; 631/45/287/1194; 631/80/128/1276; Actins - metabolism; Animals; Cattle; Cell Membrane - metabolism; Chromaffin Cells - metabolism; Exocytosis; Humanities and Social Sciences; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; multidisciplinary; PC12 Cells; Phosphatidylinositol 4,5-Diphosphate - metabolism; Protein Transport; Rats; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms1500

Neurosecretory vesicles undergo docking and priming before Ca 2+ -dependent fusion with the plasma membrane. Although de novo synthesis of phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5) P 2 ) 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) P 2 , leading to a potentiation of exocytosis in chromaffin cells. We then exploit this pathway to examine the effect of a transient PtdIns(4,5) P 2 increase on neurosecretory vesicles behaviour, outside the context of a secretagogue stimulation. Our results demonstrate that a rise in PtdIns(4,5) P 2 is sufficient to promote the mobilization and recruitment of secretory vesicles to the plasma membrane via Cdc42-mediated actin reorganization. PtdIns(4,5) P 2 , therefore, orchestrates the actin-based conveyance of secretory vesicles to the plasma membrane. The role of phosphatidylinositol(4,5)bisphosphate in exocytosis is unclear. This study shows that inhibition of the p110δ isoform of PI3-kinase promotes a transient increase in phosphatidylinositol(4,5)bisphosphate, leading to a potentiation of exocytosis in chromaffin cells.