PIKfyve Negatively Regulates Exocytosis in Neurosecretory Cells

Osborne, Shona L., Wen, Peter J., Boucheron, Christine, Nguyen, Hao N., Hayakawa, Masahiko, Kaizawa, Hiroyuki, Parker, Peter J., Vitale, Nicolas and Meunier, Frederic A. (2008) PIKfyve Negatively Regulates Exocytosis in Neurosecretory Cells. Journal of Biological Chemistry, 283 5: 2804-2813. doi:10.1074/jbc.M704856200

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Author Osborne, Shona L.
Wen, Peter J.
Boucheron, Christine
Nguyen, Hao N.
Hayakawa, Masahiko
Kaizawa, Hiroyuki
Parker, Peter J.
Vitale, Nicolas
Meunier, Frederic A.
Title PIKfyve Negatively Regulates Exocytosis in Neurosecretory Cells
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2008-02-01
Year available 2007
Sub-type Article (original research)
DOI 10.1074/jbc.M704856200
Open Access Status File (Publisher version)
Volume 283
Issue 5
Start page 2804
End page 2813
Total pages 10
Editor H. Habor
Place of publication Bethesda, MD, U.S.A.
Publisher American Society for Biochemistry and Molecular Biology, Inc.
Collection year 2008
Language eng
Subject C1
270100 Biochemistry and Cell Biology
730104 Nervous system and disorders
270105 Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)
Abstract Regulated secretion depends upon a highly co-ordinated series of protein-protein and protein-lipid interactions. Two phosphoinositides, PtdIns(4,5)P2 and PtdIns(3)P, are important for the ATP-dependent priming of the secretory apparatus prior to Ca2+-dependent exocytosis. Mechanisms that control phosphoinositides levels are likely to play an important role in priming fine-tuning. Here we have investigated the involvement of PIKfyve, a phosphoinositide 5-kinase that can phosphorylate PtdIns(3)P to produce PtdIns(3,5)P2, on large dense core vesicle exocytosis from neuroendocrine cells. PIKfyve localises to a sub-population of secretory granules in chromaffin and PC12 cells. Nicotine stimulation promoted recruitment of PIKfyve-EGFP onto secretory vesicles in PC12 cells. YM-201636, a selective inhibitor of PIKfyve activity, and PIKfyve knock-down by siRNA potentiated secretory granule exocytosis. Over-expression of PIKfyve or its yeast orthologue Fab1p inhibited regulated secretion in PC12 cells while a catalytically inactive PIKfyve mutant had no effect. These results demonstrate a novel inhibitory role for PIKfyve catalytic activity in regulated secretion and provide further evidence for a fine-tuning of exocytosis by 3-phosphorylated phospho notinositides.
Keyword Calcium
Nucleic acids
Phosphoric acid
Q-Index Code C1
Q-Index Status Confirmed Code
Additional Notes First Published on November 26, 2007

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Created: Thu, 24 Apr 2008, 09:40:13 EST by Timothy Hazelton on behalf of School of Biomedical Sciences