Interaction Between Cav2.1α1 and CaMKII in Cav2.1α1 Mutant Mice, Rolling Nagoya

Abstract

It has been reported earlier that interactions between Cav2.1α1 and calcium/calmodulin-dependent protein kinase II (CaMKII) in the presynaptic fraction and between the NMDA receptor subunit NR2B and CaMKII in the postsynaptic density (PSD) fraction are important for neuronal function. Cav2.1α1, CaMKII, and NR2B are predominantly expressed in the hippocampus. To examine the above interactions and CaMKII activity in the hippocampal presynapse and PSD of Rolling Nagoya mice carrying a mutation in Cav2.1α1 subunit, we performed immunoprecipitation and Western blot analyses. In the presynapse, the interaction between Cav2.1α1 and CaMKII and the phosphorylation of CaMKII (at Thr286) and its substrate Synapsin I (at Ser603) were decreased in mutant mice compared to wild-type mice. In the PSD, a similar pattern was observed for the interaction between NR2B and CaMKII and the phosphorylation of CaMKII (at Thr286) and its substrate AMPA receptor subunit glutamate receptor 1 (at Ser831) between mutant and wild-type mice. Our data indicate that disruption of the interaction between Cav2.1α1 and CaMKII may down-regulate presynaptic CaMKII activity and that Rolling Nagoya mice would be a useful model for examining presynaptic function.