First Author | Borgesius NZ | Year | 2011 |
Journal | J Neurosci | Volume | 31 |
Issue | 28 | Pages | 10141-8 |
PubMed ID | 21752990 | Mgi Jnum | J:174521 |
Mgi Id | MGI:5139929 | Doi | 10.1523/JNEUROSCI.5105-10.2011 |
Citation | Borgesius NZ, et al. (2011) betaCaMKII plays a nonenzymatic role in hippocampal synaptic plasticity and learning by targeting alphaCaMKII to synapses. J Neurosci 31(28):10141-8 |
abstractText | The calcium/calmodulin-dependent kinase type II (CaMKII) holoenzyme of the forebrain predominantly consists of heteromeric complexes of the alphaCaMKII and betaCaMKII isoforms. Yet, in contrast to alphaCaMKII, the role of betaCaMKII in hippocampal synaptic plasticity and learning has not been investigated. Here, we compare two targeted Camk2b mouse mutants to study the role of betaCaMKII in hippocampal function. Using a Camk2b(-/-) mutant, in which betaCaMKII is absent, we show that both hippocampal-dependent learning and Schaffer collateral-CA1 long-term potentiation (LTP) are highly dependent upon the presence of betaCaMKII. We further show that betaCaMKII is required for proper targeting of alphaCaMKII to the synapse, indicating that betaCaMKII regulates the distribution of alphaCaMKII between the synaptic pool and the adjacent dendritic shaft. In contrast, localization of alphaCaMKII, hippocampal synaptic plasticity and learning were unaffected in the Camk2b(A303R) mutant, in which the calcium/calmodulin-dependent activation of betaCaMKII is prevented, while the F-actin binding and bundling property is preserved. This indicates that the calcium/calmodulin-dependent kinase activity of betaCaMKII is fully dispensable for hippocampal learning, LTP, and targeting of alphaCaMKII, but implies a critical role for the F-actin binding and bundling properties of betaCaMKII in synaptic function. Together, our data provide compelling support for a model of CaMKII function in which alphaCaMKII and betaCaMKII act in concert, but with distinct functions, to regulate hippocampal synaptic plasticity and learning. |