Modulation of neuronal phospholipase D activity under depolarizing conditions

FEBS Letters

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