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

作者：Wen Peter J; O**orne Shona L; Zanin Mark; Low Pei Ching; Wang Hai Tao A; Schoenwaelder Simone M; Jackson Shaun P; Wedlich Soeldner Roland; Vanhaesebroeck Bart; Keating Damien J; Meunier Frederic A^*

来源：Nature Communications, 2011, 2(1): 491.

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 p110 delta 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.

• 出版日期2011-10