Literature DB >> 16055506

Phosphatidylinositol 3-kinase C2alpha is essential for ATP-dependent priming of neurosecretory granule exocytosis.

Frédéric A Meunier1, Shona L Osborne, Gerald R V Hammond, Frank T Cooke, Peter J Parker, Jan Domin, Giampietro Schiavo.   

Abstract

Neurotransmitter release and hormonal secretion are highly regulated processes culminating in the calcium-dependent fusion of secretory vesicles with the plasma membrane. Here, we have identified a role for phosphatidylinositol 3-kinase C2alpha (PI3K-C2alpha) and its main catalytic product, PtdIns3P, in regulated exocytosis. In neuroendocrine cells, PI3K-C2alpha is present on a subpopulation of mature secretory granules. Impairment of PI3K-C2alpha function specifically inhibits the ATP-dependent priming phase of exocytosis. Overexpression of wild-type PI3K-C2alpha enhanced secretion, whereas transfection of PC12 cells with a catalytically inactive PI3K-C2alpha mutant or a 2xFYVE domain sequestering PtdIns3P abolished secretion. Based on these results, we propose that production of PtdIns3P by PI3K-C2alpha is required for acquisition of fusion competence in neurosecretion.

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Year:  2005        PMID： 16055506      PMCID： PMC1237087          DOI： 10.1091/mbc.e05-02-0171

Source DB:  PubMed          Journal:  Mol Biol Cell        ISSN： 1059-1524            Impact factor:   4.138


  60 in total

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Authors:  A Brunet; S R Datta; M E Greenberg
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Journal:  J Physiol Paris       Date:  1995

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Journal:  J Neurosci       Date:  1995-02       Impact factor: 6.167

6.  ATP-dependent inositide phosphorylation required for Ca(2+)-activated secretion.

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Journal:  Nature       Date:  1995-03-09       Impact factor: 49.962

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Journal:  EMBO J       Date:  1996-05-01       Impact factor: 11.598

8.  Synaptotagmin: a membrane constituent of neuropeptide-containing large dense-core vesicles.

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Authors:  J C Hay; T F Martin
Journal:  Nature       Date:  1993-12-09       Impact factor: 49.962
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  38 in total

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Review 2.  The emerging mechanisms of isoform-specific PI3K signalling.

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4.  A new approach to the molecular analysis of docking, priming, and regulated membrane fusion.

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Journal:  J Chem Biol       Date:  2011-02-08

5.  Abrogating Munc18-1-SNARE complex interaction has limited impact on exocytosis in PC12 cells.

Authors:  Nancy T Malintan; Tam H Nguyen; Liping Han; Catherine F Latham; Shona L Osborne; Peter J Wen; Siew Joo Tiffany Lim; Shuzo Sugita; Brett M Collins; Frederic A Meunier
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8.  Secretagogue stimulation enhances NBCe1 (electrogenic Na(+)/HCO(3)(-) cotransporter) surface expression in murine colonic crypts.

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10.  Impaired dense core vesicle maturation in Caenorhabditis elegans mutants lacking Rab2.

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