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Nat Commun ; 2: 491, 2011 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-21971506

RESUMO

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.


Assuntos
Actinas/metabolismo , Células Cromafins/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Animais , Bovinos , Membrana Celular/metabolismo , Exocitose , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Células PC12 , Transporte Proteico , Ratos
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