Ca2+-regulated pool of phosphatidylinositol-3-phosphate produced by phosphatidylinositol 3-kinase C2α on neurosecretory vesicles

Wen, Peter, Osborne, Shona L., Morrow, Isabel C., Parton, Robert G., Domin, Jan and Meunier, Frederic A. (2008) Ca2+-regulated pool of phosphatidylinositol-3-phosphate produced by phosphatidylinositol 3-kinase C2α on neurosecretory vesicles. Molecular Biology of the Cell, 19 12: 5593-5603. doi:10.1091/mbc.E08-06-0595

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Author Wen, Peter
Osborne, Shona L.
Morrow, Isabel C.
Parton, Robert G.
Domin, Jan
Meunier, Frederic A.
Title Ca2+-regulated pool of phosphatidylinositol-3-phosphate produced by phosphatidylinositol 3-kinase C2α on neurosecretory vesicles
Formatted title
Ca2+-regulated Pool of Phosphatidylinositol-3-phosphate Produced by Phosphatidylinositol 3-Kinase C2α on Neurosecretory Vesicles
Journal name Molecular Biology of the Cell   Check publisher's open access policy
ISSN 1059-1524
1939-4586
Publication date 2008-12
Year available 2008
Sub-type Article (original research)
DOI 10.1091/mbc.E08-06-0595
Open Access Status File (Publisher version)
Volume 19
Issue 12
Start page 5593
End page 5603
Total pages 12
Editor David Bostein
Place of publication United States
Publisher American Society for Cell Biology
Collection year 2009
Language eng
Subject 060108 Protein Trafficking
060110 Receptors and Membrane Biology
060105 Cell Neurochemistry
920111 Nervous System and Disorders
Formatted abstract
Phosphatidylinositol-3-phosphate [PtdIns(3)P] is a key player in early endosomal trafficking and is mainly produced by class III phosphatidylinositol 3-kinase (PI3K). In neurosecretory cells, class II PI3K-C2α and its lipid product PtdIns(3)P have recently been shown to play a critical role during neuroexocytosis, suggesting that two distinct pools of PtdIns(3)P might coexist in these cells. However, the precise characterization of this additional pool of PtdIns(3)P remains to be established. Using a selective PtdIns(3)P probe, we have identified a novel PtdIns(3)P-positive pool localized on secretory vesicles, sensitive to PI3K-C2α knockdown and relatively resistant to wortmannin treatment. In neurosecretory cells, stimulation of exocytosis promoted a transient albeit large increase in PtdIns(3)P production localized on secretory vesicles sensitive to PI3K-C2α knockdown and expression of PI3K-C2α catalytically inactive mutant. Using purified chromaffin granules, we found that PtdIns(3)P production is controlled by Ca2+. We confirmed that PtdIns(3)P production from recombinantly expressed PI3K-C2α is indeed regulated by Ca2+. We provide evidence that a dynamic pool of PtdIns(3)P synthesized by PI3K-C2α occurs on secretory vesicles in neurosecretory cells, demonstrating that the activity of a member of the PI3K family is regulated by Ca2+ in vitro and in living neurosecretory cells.
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Created: Mon, 09 Mar 2009, 13:42:17 EST by Debra McMurtrie on behalf of Queensland Brain Institute