CaMKAPs

Posted by Digital Strategies (Div of Comm) on Monday, June 4, 2018 in Uncategorized.

We are testing the over-arching hypothesis that the activity, localization and ultimately biological function of CaMKII are modulated by interactions with a diverse array of CaMKII-associated proteins (CaMKAPs). Our lab was the first to show that the targeting of CaMKII to neuronal postsynaptic densities is dynamically regulated by the activation and autophosphorylation of CaMKII, and we identified GluN2B subunits of the NMDA-type glutamate receptor (NMDAR) as the first CaMKAP and characterized the interactions in detail. This interaction significantly contributes to CaMKII targeting in dendritic spines, and is necessary for normal synaptic plasticity. As additional examples, we have shown that another CaMKAP, densin, can inhibit CaMKII phosphorylation of GluA1 AMPA-type glutamate receptor subunits, but not of GluN2B. In contrast, alpha-actinin can partially activate CaMKII binding to and phosphorylation of GluN2B, but not of GluA1. Our recent proteomics studies identifed over 100 proteins associated directly or indirectly with synaptic CaMKII holoenzymes, including several other proteins linked to autism spectrum disorders. Thus, we are working on the idea that numerous subpopulations of CaMKII holoenzymes, associated with distinct CaMKAPs play distinct physiological and pathophysiological roles.