βCaMKII plays a nonenzymatic role in hippocampal synaptic plasticity and learning by targeting α;CaMKII to synapses
The calcium/calmodulin-dependent kinase type II (CaMKII) holoenzyme of the forebrain predominantly consists of heteromeric complexes of the αCaMKII andβCaMKII isoforms. Yet, in contrast toβCaMKII, the role of βCaMKII in hippocampal synaptic plasticity and learning has not been investigated. Here, we compare two targeted Camk2b mouse mutants to study the role of αCaMKII in hippocampal function. Using a Camk2b-1-mutant, in which βCaMKII is absent, we show that both hippocampal-dependent learning and Schaffer collateralβCA1 long-term potentiation (LTP) are highly dependent upon the presence of β Ca MKII. We further show that αCaMKII is required for proper targeting of β Ca MKII to the synapse, indicating that βCaMKII regulates the distribution of αCa M KII between the synaptic pool and the adjacent dendritic shaft. In contrast, localization of β Ca MKII, hippocampal synaptic plasticity and learning were unaffected in the Camk2bA303Rmutant, in which the calcium/calmodulin-dependent activation of βCaMKII is prevented, while the F-actin binding and bundling property is preserved. This indicates that the calcium/calmodulin-dependent kinase activity of αCaMKII is fully dispensable for hippocampal learning, LTP, and targeting of βCaMKII, but implies a critical role for the F-actin binding and bundling properties of βCaMKII in synaptic function. Together, our data provide compelling support for a model of CaMKII function in which βCaMKII and βCaMKII act in concert, but with distinct functions, to regulate hippocampal synaptic plasticity and learning.
|Persistent URL||dx.doi.org/10.1523/JNEUROSCI.5105-10.2011, hdl.handle.net/1765/31481|
Borgesius, N.Z., van Woerden, G.M., Buitendijk, G.H.S., Keijzer, N., Jaarsma, D., Hoogenraad, C.C., & Elgersma, Y.. (2011). βCaMKII plays a nonenzymatic role in hippocampal synaptic plasticity and learning by targeting α;CaMKII to synapses. The Journal of Neuroscience, 31(28), 10141–10148. doi:10.1523/JNEUROSCI.5105-10.2011