Phosphatidylinositol 3-Kinase C2α Is Essential for ATP-dependent Priming of Neurosecretory Granule Exocytosis-Reference-Cited by-同舟云学术

Phosphatidylinositol 3-Kinase C2α Is Essential for ATP-dependent Priming of Neurosecretory Granule Exocytosis

Published:2005-10 Issue:10 Volume:16 Page:4841-4851
ISSN:1059-1524
Container-title:Molecular Biology of the Cell
language:en
Short-container-title:MBoC

Author:

Meunier Frédéric A.¹²,Osborne Shona L.²,Hammond Gerald R.V.¹,Cooke Frank T.³,Parker Peter J.¹,Domin Jan⁴,Schiavo Giampietro¹

Affiliation:

1. Lincoln's Inn Fields Laboratories, London Research Institute, Cancer Research UK, London WC2A 3PX, United Kingdom

2. Molecular Dynamics of Synaptic Function Laboratory, School of Biomedical Sciences, University of Queensland, St. Lucia, 4072 Queensland, Australia

3. Biochemistry and Molecular Biology, University College London, WC1E 6BT London, United Kingdom

4. Renal Section, Faculty of Medicine, Imperial College, London W12 0NN, United Kingdom

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 C2α (PI3K-C2α) and its main catalytic product, PtdIns3P, in regulated exocytosis. In neuroendocrine cells, PI3K-C2α is present on a subpopulation of mature secretory granules. Impairment of PI3K-C2α function specifically inhibits the ATP-dependent priming phase of exocytosis. Overexpression of wild-type PI3K-C2α enhanced secretion, whereas transfection of PC12 cells with a catalytically inactive PI3K-C2α mutant or a 2xFYVE domain sequestering PtdIns3P abolished secretion. Based on these results, we propose that production of PtdIns3P by PI3K-C2α is required for acquisition of fusion competence in neurosecretion.

Publisher

American Society for Cell Biology (ASCB)

Subject

Cell Biology,Molecular Biology

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