Take our Survey

Reference: Osborne SL, et al. (2008) PIKfyve Negatively Regulates Exocytosis in Neurosecretory Cells. J Biol Chem 283(5):2804-2813

Reference Help

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 phosphoinositides.

Reference Type
Journal Article
Authors
Osborne SL, Wen PJ, Boucheron C, Nguyen HN, Hayakawa M, Kaizawa H, Parker PJ, Vitale N, Meunier FA
Primary Lit For
Additional Lit For
Review For

Interaction Annotations

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Type Assay Annotation Action Modification Phenotype Source Reference

Gene Ontology Annotations

Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Gene Ontology Term Qualifier Aspect Method Evidence Source Assigned On Annotation Extension Reference

Phenotype Annotations

Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Regulation Annotations

Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Experiment Assay Construct Conditions Strain Background Reference