Brain-derived neurotrophic factor increases Ca2+/calmodulin-dependent protein kinase 2 activity in hippocampus.
Here we show that brain-derived neurotrophic factor (BDNF) stimulates both the phosphorylation of the Ca2+/calmodulin-dependent protein kinase 2 (CaMK2) and its kinase activity in rat hippocampal slices. In addition, we find that: (i) the time course of BDNF action is not accompanied by a change in the spectrum of either alpha- and beta-subunits of CaMK2 detected by immunoblotting; (ii) both treatment of solubilized CaMK2 with alkaline phosphatase and treatment of immunoprecipitated CaMK2 with protein phosphatase 1 reverse phosphorylation and activation of the kinase; (iii) phospholipase C inhibitor D609 and intracellular Ca2+ chelation by 1,2-bis-(o-aminophenoxy)ethane-N,N,N",N',-tetracetic acid tetra(acetoxymethyl)ester or 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate but not omission of Ca2+ or Ca2+ chelation by EGTA, abolish the stimulatory effect of BDNF on phosphorylation and activation of CaMK2. These results strongly suggest that the conversion of CaMK2 into its active, autophosphorylated form, but not its concentration, is increased by BDNF via stimulation of phospholipase C and subsequent intracellular Ca2+ mobilization.
Blanquet
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Unité de Recherche de Physiopharmacologie du Système Nerveux, U-161 INSERM, 2 rue d'Alésia, 75014 Paris, France.
Lamour
Y
Y
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D008297:Male; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010738:Type C Phospholipases