title: Ca2+-independent activation of Ca2+/calmodulin-dependent protein kinase II bound to the C-terminal domain of CaV2.1 calcium channels.
abstract: Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) forms a major component of the postsynaptic density where its functions in synaptic plasticity are well established, but its presynaptic actions are poorly defined. Here we show that CaMKII binds directly to the C-terminal domain of Ca(V)2.1 channels. Binding is enhanced by autophosphorylation, and the kinase-channel signaling complex persists after dephosphorylation and removal of the Ca(2+)/CaM stimulus. Autophosphorylated CaMKII can bind the Ca(V)2.1 channel and synapsin-1 simultaneously. CaMKII binding to Ca(V)2.1 channels induces Ca(2+)-independent activity of the kinase, which phosphorylates the enzyme itself as well as the neuronal substrate synapsin-1. Facilitation and inactivation of Ca(V)2.1 channels by binding of Ca(2+)/CaM mediates short term synaptic plasticity in transfected superior cervical ganglion neurons, and these regulatory effects are prevented by a competing peptide and the endogenous brain inhibitor CaMKIIN, which blocks binding of CaMKII to Ca(V)2.1 channels. These results define the functional properties of a signaling complex of CaMKII and Ca(V)2.1 channels in which both binding partners are persistently activated by their association, and they further suggest that this complex is important in presynaptic terminals in regulating protein phosphorylation and short term synaptic plasticity.
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA.
authors.forename: Venkat G
authors.initials: VG
authors.lastname: Magupalli
authors.forename: Sumiko
authors.initials: S
authors.lastname: Mochida
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Westenbroek
authors.forename: Angus C
authors.initials: AC
authors.lastname: Nairn
authors.forename: Todd
authors.initials: T
authors.lastname: Scheuer
authors.forename: William A
authors.initials: WA
authors.lastname: Catterall
mesh_terms: D020864:Calcium Channels, N-Type / Q000737:chemistry*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D004594:Electrophysiology / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D009473:Neuronal Plasticity; D018377:Neurotransmitter Agents / Q000378:metabolism; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D014162:Transfection
chemical_list: D020864:Calcium Channels, N-Type; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D018377:Neurotransmitter Agents; D011994:Recombinant Proteins