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- W1974189321 abstract "Abstract: Ca+2/calmodulin-dependent protein kinase II (CaMKII) forms a major component of postsynaptic density, where its functions are well established but the presynaptic actions of CaMKII are poorly defined. We show that CaMKII constitutively binds and modulates presynaptic voltage-gated calcium (Cav2.1) channels that conduct P/Q type calcium currents. Using co-immunoprecipitation methods, we isolated a signaling complex of Cav2.1 with bound CaMKII. The pore-forming 1 subunit of Cav2.1 channels offers a unique platform for association of CaMKII at the C-terminal domain. The Cav2.1/CaMKII signaling complex operates as a network of multiprotein machines by recruiting other protein components and processing information by a series of protein interactions and protein phosphorylation reactions. Using GST pulldown assays we dissected the preferential binding of the inactive kinase to the Cav2.1 channel and mapped the binding site. Binding of CaMKII at this site per se is sufficient to slow voltage-dependent inactivation and shift the voltage dependence of inactivation to more positive membrane potentials, thereby greatly enhancing Cav2.1 channel activity. Using transfection assays, we show that the bound kinase is autophosphorylated at Thr286 and phosphorylates synapsin 1. We observed more than a six-fold increase in the synapsin 1 phosphorylation by CaMKII bound to the C-terminal domain Cav2.1 channel. Synapsin phosphorylation at Ser603 by CaMKII leads to formation of stable higher order oligomers. Our studies reveal a signaling complex of Cav2.1/CaMKII at the C-terminal domain of the Cav2.1 channel. Association of CaMKII with this signaling complex generates rapid response to calcium entry, recruitment of protein components, and phosphorylation of nearby proteins. Hence, kinase couples calcium influx to the downstream pathways for rapid, localized signal transduction and regulation. Supported by R01 NS22625" @default.
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- W1974189321 date "2011-02-01" @default.
- W1974189321 modified "2023-09-26" @default.
- W1974189321 title "Signaling Complex of Calcium/Calmodulin-Dependent Protein Kinase II Associated with the C-Terminal Domain of CaV2.1 Channels" @default.
- W1974189321 doi "https://doi.org/10.1016/j.bpj.2010.12.3305" @default.
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