Calcium‐Calmodulin Dependent Kinase II (CaMKII) N‐methyl D‐aspartate Receptors (NMDAR) Interactions in Development and Disease

Abstract

Postsynaptic CaMKII translates dynamic changes in local calcium concentrations into diverse functional responses. Proper CaMKII localization, phosphorylation, and activity are crucial for long‐term potentiation as well as normal learning and memory, and are disrupted in animal models of multiple neurological diseases (van Woerden et al., 2007). To determine how changes in CaMKII expression and phosphorylation over a developmental timeline (rodent postnatal day: 7, 25, 90) affects its interactions with CaMKII‐associated proteins (CaMKAPs), we have developed a fractionation protocol which allows us to probe interactions in cytosolic, membrane‐associated, and post‐synaptic density (PSD)‐associated pools of proteins. Both CaMKII and NMDAR subunits are present in multiple subcellular compartments, but a complex of these proteins can only be co‐immunoprecipitated from the PSD pool. In addition, CaMKII differentially interacts with NMDAR subunits across the developmental timeline. Other CaMKAPs that modulate CaMKII localization and activation are also being explored. Ultimately, we will determine how these interactions are disrupted in mouse disease models that exhibit hyperphosphorylation of CaMKII (i.e. Angelman Syndrome, Parkinson's Disease) as well as other models of altered CaMKII phosphorylation (T286A CaMKII knockin mice).