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  • Title: Differential stimulus-dependent synaptic recruitment of CaMKIIα by intracellular determinants of GluN2B.
    Author: She K, Rose JK, Craig AM.
    Journal: Mol Cell Neurosci; 2012 Nov; 51(3-4):68-78. PubMed ID: 22902837.
    Abstract:
    The calcium-calmodulin activated kinase CaMKII mediates many forms of learning and memory. Activity-regulated translocation of CaMKII to synapses is important for its functions in synaptic plasticity. Here, we tested the role of the NMDA receptor subunit GluN2B in recruiting CaMKIIα to synapses with different paradigms: global bath stimulation of NMDA receptors, a chemical long term potentiation (cLTP) protocol that selectively activates synaptic NMDA receptors, or local stimulation of NMDA receptors at a contiguous set of ~10-30 synapses that triggers a propagating synaptic accumulation of CaMKII. Global or cLTP-induced synaptic accumulation of CaMKIIα occurred in wild-type but not sister GluN2B -/- cultured mouse hippocampal neurons. Expression of YFP-GluN2B, but not a similar level of YFP-GluN2A, rescued global and cLTP-induced CaMKIIα translocation. Using chimeric constructs, the pore-forming extracellular and membrane domains of GluN2A combined with the cytoplasmic tail of GluN2B were sufficient to rescue CaMKIIα translocation, whereas the reverse chimera was ineffective. Furthermore, the dual point mutation R1300Q,S1303D in GluN2B that blocks interaction of this high affinity site with CaMKII abolished rescue. Thus, CaMKII binding to GluN2B is required for global and cLTP-induced synaptic accumulation of CaMKIIα. However, surprisingly, locally induced propagating synaptic accumulation of CaMKIIα occurred normally in GluN2B -/- neurons, indistinguishably from wild-type. Thus, synaptic trapping of CaMKII during locally induced propagating translocation occurs by different mechanisms and molecular partners compared with global stimulation and cLTP paradigms. These findings underscore the complex regulatory properties and molecular interactions of CaMKIIα, a key player in synaptic plasticity.
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