RT Journal Article
SR Electronic
T1 βCaMKII Plays a Nonenzymatic Role in Hippocampal Synaptic Plasticity and Learning by Targeting αCaMKII to Synapses
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10141
OP 10148
DO 10.1523/JNEUROSCI.5105-10.2011
VO 31
IS 28
A1 Nils Z. Borgesius
A1 Geeske M. van Woerden
A1 Gabrielle H. S. Buitendijk
A1 Nanda Keijzer
A1 Dick Jaarsma
A1 Casper C. Hoogenraad
A1 Ype Elgersma
YR 2011
UL http://www.jneurosci.org/content/31/28/10141.abstract
AB The calcium/calmodulin-dependent kinase type II (CaMKII) holoenzyme of the forebrain predominantly consists of heteromeric complexes of the αCaMKII and βCaMKII isoforms. Yet, in contrast to αCaMKII, 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 βCaMKII in hippocampal function. Using a Camk2b−/− mutant, in which βCaMKII is absent, we show that both hippocampal-dependent learning and Schaffer collateral–CA1 long-term potentiation (LTP) are highly dependent upon the presence of βCaMKII. We further show that βCaMKII is required for proper targeting of αCaMKII to the synapse, indicating that βCaMKII regulates the distribution of αCaMKII between the synaptic pool and the adjacent dendritic shaft. In contrast, localization of αCaMKII, hippocampal synaptic plasticity and learning were unaffected in the Camk2bA303R mutant, 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 βCaMKII is fully dispensable for hippocampal learning, LTP, and targeting of αCaMKII, 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 αCaMKII and βCaMKII act in concert, but with distinct functions, to regulate hippocampal synaptic plasticity and learning.