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The transient release of βCa MKII from F-actin may be important for reorganization of the cytoskeleton to enable remodeling of the dendritic spine (Okamoto et al.2009), which appears necessary for late LTP and long-term memory (LTM) (e.g., Fukazawa et al. As well as binding F-actin, βCa MKII unbound to calcium/calmodulin can also target the immediate-early gene Arc/Arg3.1 to inactive synapses where it promotes endocytosis of AMPA receptor subunits, which leads to synaptic depression (Okuno et al. It remains to be tested whether this Arc/Arg3.1 localization contributes to memory formation.Activated Ca MKII phosphorylates the stargazin subunit of AMPA receptor (AMPAR) complexes enabling AMPARs to translocate to the postsynaptic density (PSD).
1998) and blockade of Ca MKII substantially impairs memory formation (for reviews, see Lisman et al. 1992a,b), but these mutants have a milder phenotype than αCa MKII knockin (KI) mice with impaired calcium/calmodulin binding due to compensatory translocation of βCa MKII into synapses (Elgersma et al. Furthermore, transgenic expression of a constitutively active form of αCa MKII leads to unwanted secondary changes in gene expression (Bejar et al. Model of the role of Ca MKII in synaptic potentiation underlying memory formation.Binding of calcium/calmodulin to βCa MKII dissociates the kinase from F-actin (Lin and Redmond 2008), allowing Ca MKII to translocate to the postsynaptic density (Shen and Meyer 1999).F-actin binding is essential for hippocampus-dependent contextual fear memory formation and for targeting Ca MKII holoenzymes to dendritic spines (Borgesius et al. In contrast, the kinase activity of βCa MKII is not required for contextual fear memory formation (Borgesius et al. Thus, βCa MKII has a nonenzymatic role in memory formation.These kinases have different targets and they differ in their activation properties.
A small subset of these kinases has been implicated in learning and memory.
This will also allow for a systematic analysis of dysfunctional kinase activity in mental disorders.