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PMID: 16055506 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Molecular biology of the cell ·Vol. 16 ·No. 10 ·2005-10-00 ·Pages 4841-51

Meunier FA, Osborne SL, Hammond GR, Cooke FT, Parker PJ, Domin J, Schiavo G

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.

MeSH Terms
Adenosine Triphosphate/metabolism Adrenal Glands/cytology Animals Catecholamines/metabolism Cattle Cells, Cultured Chromaffin Cells/physiology Class II Phosphatidylinositol 3-Kinases Exocytosis/physiology Human Growth Hormone/metabolism Humans Mutation Neurosecretion/physiology Phosphatidylinositol 3-Kinases/genetics,metabolism Phosphatidylinositol Phosphates/metabolism Rats Secretory Vesicles/physiology
Chemicals
Catecholamines Phosphatidylinositol Phosphates phosphatidylinositol 3-phosphate Human Growth Hormone Adenosine Triphosphate Phosphatidylinositol 3-Kinases Class II Phosphatidylinositol 3-Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Meunier Frédéric A
Lincoln's Inn Fields Laboratories, London Research Institute, Cancer Research UK, London WC2A 3PX, United Kingdom.
Osborne Shona L
Hammond Gerald R V
Cooke Frank T
Parker Peter J
Domin Jan
Schiavo Giampietro
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e05-02-0171
Published
2005-10-00
Epub
2005-00-29
Pages
4841-51
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC1237087
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1091/mbc.e05-02-0171 PMC Full Text View journal details
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