CaMKII-The "Memory" Molecule
CaMKII is a Mutli-subunit Enzyme Serving Enzymatic and Scaffolding Roles
CaMKII is composed of 12 catalytically active subunits. Using stain and cryo-electron microscopy our lab established the first 3D structure of the CaMKII holoenzyme shown in the pseudo-colored image at the right. The gear shaped association domain (yellow) holds the 12 subunits together leaving the unusual situation of having the catalytic domains (blue) extend outwards from the core in two rings of six subunits above and below the core. The proximity of the catalytic domains facilitates autophosphorylation of the subunits following Ca2+/CaM activation. Autophosphorylation sustains enzyme activity after the activating signal (elevated Ca2+) has returned to resting levels, a property fundamental to a "memory molecule".
CaMKII is Highly Concentrated in Synaptic Spines
CaMKII is one of the most abundant proteins at synapses and serves both enzymatic (phosphorylation) and structural roles. We are defining how CaMKII is activated, how is it recruited to active synapses and which synaptic proteins it interacts with. The figure at left is a hippocampal neuron cultured for 21 days in vitro stained with an antibody to CaMKII (in green) and to synapsin 1 (in red) a presynaptic protein associated with synaptic vesicles. Note the synaptic spines extending from the dendrite enriched for CaMKII, with each spine making contact with a synapsin 1 containing presynaptic terminal.
CaMKII is a Synaptic Scaffolding Protein
The multisubunit nature of CaMKII provides an ideal architecture for a scaffold protein. The geometry of CaMKII provides unique (20 nm) spacing between other interacting proteins. We showed that CaMKII interacts with F-actin (and G-actin) to control the assembly and architecture of the actin cytoskeleton. The image at right shows an electron micrograph of CaMKII and actin assemblies formed on a lipid monolayer to produce well organized 2D superstructures. The enzyme (red circles) is clearly evident bridging actin filaments. The quality of the image is sufficient to see individual actin monomers in their characteristic twisted organization within the filaments.
