title: Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells.
abstract: 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.
authors.affiliation: The University of Queensland, Queensland Brain Institute and School of Biomedical Sciences, Brisbane, Queensland 4072, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wen
authors.forename: Shona L
authors.initials: SL
authors.lastname: Osborne
authors.forename: Mark
authors.initials: M
authors.lastname: Zanin
authors.forename: Pei Ching
authors.initials: PC
authors.lastname: Low
authors.forename: Hai-Tao A
authors.initials: HT
authors.lastname: Wang
authors.forename: Simone M
authors.initials: SM
authors.lastname: Schoenwaelder
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Jackson
authors.forename: Roland
authors.initials: R
authors.lastname: Wedlich-Söldner
authors.forename: Bart
authors.initials: B
authors.lastname: Vanhaesebroeck
authors.forename: Damien J
authors.initials: DJ
authors.lastname: Keating
authors.forename: Frédéric A
authors.initials: FA
authors.lastname: Meunier
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D019439:Chromaffin Cells / Q000378:metabolism*; D005089:Exocytosis; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D016716:PC12 Cells; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats
chemical_list: D000199:Actins; D019269:Phosphatidylinositol 4,5-Diphosphate