Calcium/calmodulin-dependent protein kinase II (CaMKII) is an essentially ubiquitous, dodecameric, serine/threonine protein kinase that is expressed in multiple isoforms. Many studies have revealed that CaMKII plays an essential role in the molecular mechanisms of learning and memory. Though multiple techniques have been utilized to demonstrate that CaMKII presence, regulation, and activity contribute to synaptic plasticity, localization and anchoring of the kinase have not been directly linked to this phenomenon. It is my goal to demonstrate, through the use of biochemistry, cell culture, and electrophysiology, that CaMKII anchoring contributes to the synaptic plasticity of the CA1 region of the hippocampus. Hypothesis: CaMKII anchoring at the synapse is dependant on interactions with densin-180, a-actinin, and/or NR2B, and some or all of these interactions are necessary for normal expression of synaptic plasticity in hippocampal neurons.
Three specific aims address this hypothesis: 1) To define the minimal CaMKII-binding region of a-actinin and examine the regulation of this binding; 2) to determine the ability of densin-180, a-actinin, and NR2B binding regions to disrupt CaMKII localization in cultured neurons; and 3) to determine the effects of CaMKII mislocalization on synaptic function in the hippocampus.
| Jiao, Yuxia; Jalan-Sakrikar, Nidhi; Robison, A J et al. (2011) Characterization of a central Ca2+/calmodulin-dependent protein kinase IIalpha/beta binding domain in densin that selectively modulates glutamate receptor subunit phosphorylation. J Biol Chem 286:24806-18 |
| Jiao, Yuxia; Robison, A J; Bass, Martha A et al. (2008) Developmentally regulated alternative splicing of densin modulates protein-protein interaction and subcellular localization. J Neurochem 105:1746-60 |
| Robison, A J; Bartlett, Ryan K; Bass, Martha A et al. (2005) Differential modulation of Ca2+/calmodulin-dependent protein kinase II activity by regulated interactions with N-methyl-D-aspartate receptor NR2B subunits and alpha-actinin. J Biol Chem 280:39316-23 |
| Robison, A J; Bass, Martha A; Jiao, Yuxia et al. (2005) Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2. J Biol Chem 280:35329-36 |
