Okamoto K-I, Narayanan R, Lee SH, Murata K, Hayashi Y. The role of CaMKII as an F-actin-bundling protein crucial for maintenance of dendritic spine structure. PNAS 104: 6418-6423

RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 04/2007; 104(15):6418-23. DOI: 10.1073/pnas.0701656104
Source: PubMed


Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine protein kinase critically involved in synaptic plasticity in the brain. It is highly concentrated in the postsynaptic density fraction, exceeding the amount of any other signal transduction molecules. Because kinase signaling can be amplified by catalytic reaction, why CaMKII exists in such a large quantity has been a mystery. Here, we provide biochemical evidence that CaMKII is capable of bundling F-actin through a stoichiometric interaction. Consistent with this evidence, in hippocampal neurons, RNAi-mediated down-regulation of CaMKII leads to a reduction in the volume of dendritic spine head that is mediated by F-actin dynamics. An overexpression of CaMKII slowed down the actin turnover in the spine head. This activity was associated with beta subunit of CaMKII in a manner requiring its actin-binding and association domains but not the kinase domain. This finding indicates that CaMKII serves as a central signaling molecule in both functional and structural changes during synaptic plasticity.

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    • "CaMKIIβ has a higher affinity for Ca 2+ /CaM than CaMKIIα. Also, through a specific sequence between regulatory and association domains, CaMKIIβ interacts with F-actin whereas the α isoform does not (Okamoto et al. 2007). In an elegant set of experiments, the authors provide evidence that the different roles of the CaMKII subunits in RP are attributed to a difference in their affinities for Ca 2+ /CaM, rather than their F-actin-binding ability. "

    The Journal of Physiology 11/2014; 592(22). DOI:10.1113/jphysiol.2014.284414 · 5.04 Impact Factor
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    • "Interestingly, the α and β isoforms of CaMKII have been reported to have independent but essential functions in maintaining LTP [1], [2], [5]. CaMKIIβ may specifically affect synaptic function by altering the size and shape of the dendritic spines [6]–[8], or by localizing CaMKIIα to the dendritic spines [9]. "
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    ABSTRACT: The calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain, where it makes important contributions to synaptic organization and homeostasis, including playing an essential role in synaptic plasticity and memory. Four genes encode isoforms of CaMKII (α, β, δ, γ), with CaMKIIα and CaMKIIβ highly expressed in the brain. Decades of molecular and cellular research, as well as the use of a large number of CaMKIIα mutant mouse lines, have provided insight into the pivotal roles of CaMKIIα in brain plasticity and cognition. However, less is known about the CaMKIIβ isoform. We report the development and extensive behavioral and phenotypic characterization of a CaMKIIβ knockout (KO) mouse. The CaMKIIβ KO mouse was found to be smaller at weaning, with an altered body mass composition. The CaMKIIβ KO mouse showed ataxia, impaired forelimb grip strength, and deficits in the rotorod, balance beam and running wheel tasks. Interestingly, the CaMKIIβ KO mouse exhibited reduced anxiety in the elevated plus maze and open field tests. The CaMKIIβ KO mouse also showed cognitive impairment in the novel object recognition task. Our results provide a comprehensive behavioral characterization of mice deficient in the β isoform of CaMKII. The neurologic phenotypes and the construction of the genotype suggest the utility of this KO mouse strain for future studies of CaMKIIβ in brain structure, function and development.
    PLoS ONE 08/2014; 9(8):e105191. DOI:10.1371/journal.pone.0105191 · 3.23 Impact Factor
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    • ") and spine size and number (Okamoto et al., 2007) and prevents homeostatic upregulation of GluA1 upon chronic block of AMPAR Neuron 81, January 22, 2014 ª2014 Elsevier Inc. 259 Neuron Review activity (Groth et al., 2011). The observation that Ca 2+ channel inhibition counteracts the effect of decreased network activity on GKAP and PSD-95 is surprising, as is the increase in CaMKIIb T287 autophosphorylation upon TTX treatment, as Ca 2+ influx via L-type channels will be reduced. "
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    ABSTRACT: While CaMKII has long been known to be essential for synaptic plasticity and learning, recent work points to new dimensions of CaMKII function in the nervous system, revealing that CaMKII also plays an important role in synaptic organization. Ca(2+)-triggered autophosphorylation of CaMKII not only provides molecular memory by prolonging CaMKII activity during long-term plasticity (LTP) and learning but also represents a mechanism for autoactivation of CaMKII's multifaceted protein-docking functions. New details are also emerging about the distinct roles of CaMKIIα and CaMKIIβ in synaptic homeostasis, further illustrating the multilayered and complex nature of CaMKII's involvement in synaptic regulation. Here, I review novel molecular and functional insight into how CaMKII supports synaptic function.
    Neuron 01/2014; 81(2):249-65. DOI:10.1016/j.neuron.2013.12.024 · 15.05 Impact Factor
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