RRC ID 1228
著者 Rajebhosale M, Greenwood S, Vidugiriene J, Jeromin A, Hilfiker S.
タイトル Phosphatidylinositol 4-OH kinase is a downstream target of neuronal calcium sensor-1 in enhancing exocytosis in neuroendocrine cells.
ジャーナル J Biol Chem
Abstract Neuronal calcium sensor-1 (NCS-1), the mammalian orthologue of frequenin, belongs to a family of EF-hand-containing Ca(2+) sensors. NCS-1/frequenin has been shown to enhance synaptic transmission in PC12 cells and Drosophila and Xenopus, respectively. However, the precise molecular mechanism for the enhancement of exocytosis is largely unknown. In PC12 cells, NCS-1 potentiated exocytosis evoked by ATP, an agonist to phospholipase C-linked receptors, but had no effect on depolarization-evoked release. NCS-1 also enhanced exocytosis triggered by ionomycin, a Ca(2+) ionophore that bypasses K(+) and Ca(2+) channels. Overexpression of NCS-1 caused a shift in the dose-response curve of inhibition of ATP-evoked secretion using phenylarsine oxide, an inhibitor of phosphatidylinositol 4-OH kinase (PI4K). Plasma membrane phosphatidylinositol 4,5-bisphosphate pools were increased upon NCS-1 transfection as visualized using a phospholipase C-delta pleckstrin homology domain-green fluorescent protein construct. NCS-1-transfected cell extracts displayed increased phosphatidylinositol-4-phosphate biosynthesis, indicating an increase in PI4K activity. Mutations in NCS-1 equivalent to those that abolish the interaction of recoverin, another EF-hand-containing Ca(2+) sensor, with its downstream target rhodopsin kinase, lost their ability to enhance exocytosis. Taken together, the present data indicate that NCS-1 modulates the activity of PI4K, leading to increased levels of phosphoinositides and concomitant enhancement of exocytosis.
巻・号 278(8)
ページ 6075-84
公開日 2003-2-21
DOI 10.1074/jbc.M204702200
PII S0021-9258(20)86598-3
PMID 12471042
MeSH 1-Phosphatidylinositol 4-Kinase / antagonists & inhibitors 1-Phosphatidylinositol 4-Kinase / metabolism* Adenosine Triphosphate / pharmacology Animals Arsenicals / pharmacology Calcium Signaling / physiology Calcium-Binding Proteins / metabolism* Drosophila Enzyme Inhibitors / pharmacology Exocytosis / drug effects Exocytosis / physiology* Ionomycin / pharmacology Membrane Potentials / drug effects Neuronal Calcium-Sensor Proteins Neuropeptides / metabolism* Neurosecretory Systems / drug effects Neurosecretory Systems / physiology PC12 Cells Pheochromocytoma Rats Type C Phospholipases / metabolism Xenopus
IF 4.238
引用数 55
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 PC-12(RCB0009)