CaMKII Anchoring in Synaptic Plasticity

Vanderbilt University, Nashville TN

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Abstract

DESCRIPTION (provided by applicant): 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.