Modulation of neuronal phospholipase D activity under depolarizing conditions
| Autor: | Ulrike Kempter, Petra Seimetz, Ira Böckmann, Jan Drappatz, Mark Waring, Oksana Weichel, Elisabet Sarri, Angela Valeva, Jochen Klein |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Time Factors Biophysics chemistry.chemical_element Calcium Hippocampus Biochemistry Ouabain Membrane Potentials Potassium Chloride chemistry.chemical_compound Structural Biology Ca2+/calmodulin-dependent protein kinase Synaptosome Electrochemistry Phospholipase D Genetics medicine Animals Phospholipase D activity Enzyme Inhibitors Rats Wistar Molecular Biology Protein Kinase C Protein Synthesis Inhibitors Calcium/calmodulin-dependent protein kinase II Neomycin Depolarization Phosphatidylinositol-4 5-bisphosphate Cell Biology Rats Cell biology enzymes and coenzymes (carbohydrates) chemistry Calcium-Calmodulin-Dependent Protein Kinases lipids (amino acids peptides and proteins) Veratridine Synaptosomes medicine.drug |
| Zdroj: | FEBS Letters. 464:21-24 |
| ISSN: | 0014-5793 |
| DOI: | 10.1016/s0014-5793(99)01669-5 |
| Popis: | 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 (PIP(2)). Moreover, in synaptosomes permeabilized with Staphylococcus aureus alpha-toxin, PLD activation induced by calcium was abolished by neomycin, a PIP(2) chelator. We conclude that depolarizing conditions cause an inhibition of neuronal PLD activity which is likely due to breakdown of PIP(2), a required cofactor for PLD activity. Our findings suggest that neuronal PLD activity is regulated by synaptic activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text