FEBS Letters | |
Modulation of neuronal phospholipase D activity under depolarizing conditions | |
Böckmann, Ira2  Klein, Jochen2  Seimetz, Petra2  Valeva, Angela1  Waring, Mark2  Drappatz, Jan2  Kempter, Ulrike2  Sarri, Elisabet2  Weichel, Oksana2  | |
[1] Department of Medical Microbiology and Hygiene, University of Mainz, Obere Zahlbacher Str. 67, D-55101 Mainz, Germany;Department of Pharmacology, University of Mainz, Obere Zahlbacher Str. 67, D-55101 Mainz, Germany | |
关键词: Synaptosome; Phospholipase D; Depolarization; Calcium/calmodulin-dependent protein kinase II; Phosphatidylinositol-4; 5-bisphosphate; CaMKII; calcium/calmodulin-dependent kinase II; PC; phosphatidylcholine; PEth; phosphatidylethanol; PI; phosphatidylinositol; PIP2; phosphatidylinositol-4; 5-bisphosphate; PKC; protein kinase C; PLD; phospholipase D; PP; phosphatidylpropanol; | |
DOI : 10.1016/S0014-5793(99)01669-5 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
Neuronal phospholipase D (PLD) activity was hypothesized to be involved in vesicle trafficking and endocytosis and, possibly, transmitter release. We here report that prolonged depolarization of rat hippocampal slices by potassium chloride (KCl) or 4-aminopyridine inhibited PLD activity. Similarly, PLD activity in rat cortical synaptosomes was significantly inhibited by depolarizing agents including veratridine and ouabain. Inhibition of calcium/calmodulin kinase II (CaMKII) which positively modulates synaptosomal PLD activity [Sarri et al. (1998) FEBS Lett. 440, 287–290] by KN-62 caused a further reduction of PLD activity in depolarized synaptosomes. Depolarization-induced inhibition of PLD activity was apparently not due to transmitter release or activation of other kinases. We observed, however, that KCl-induced depolarization caused an increase of inositol phosphates and a reduction of the synaptosomal pool of phosphatidylinositol-4,5-bisphosphate (PIP2). Moreover, in synaptosomes permeabilized with Staphylococcus aureus α-toxin, PLD activation induced by calcium was abolished by neomycin, a PIP2 chelator. We conclude that depolarizing conditions cause an inhibition of neuronal PLD activity which is likely due to breakdown of PIP2, a required cofactor for PLD activity. Our findings suggest that neuronal PLD activity is regulated by synaptic activity.
【 授权许可】
Unknown
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