@article {745, title = {Autonomous CaMKII can promote either long-term potentiation or long-term depression, depending on the state of T305/T306 phosphorylation.}, journal = {J Neurosci}, volume = {30}, year = {2010}, month = {2010 Jun 30}, pages = {8704-9}, abstract = {

Ca(2+)/calmodulin-dependent kinase II (CaMKII) is a key mediator of long-term potentiation (LTP). Whereas acute intracellular injection of catalytically active CaMKII fragments saturates LTP (Lledo et al., 1995), an autonomously active form (T286D) of CaMKII holoenzyme expressed in transgenic mice did not saturate potentiation (Mayford et al., 1995). To better understand the role of the holoenzyme in the control of synaptic strength, we transfected hippocampal neurons with constructs encoding forms of CaMKII mimicking different phosphorylation states. Surprisingly, T286D not only failed to potentiate synaptic strength, but produced synaptic depression through an long-term depression (LTD)-like process. T305/T306 phosphorylation was critical for this depression because overexpression of the pseudophosphorylated form (T286D/T305D/T306D) caused depression that occluded LTD, and overexpression of an autonomous form in which T305/T306 could not be phosphorylated (T286D/T305A/T306A) prevented LTD (instead producing potentiation). Therefore, autonomous CaMKII can lead to either LTP or LTD, depending on the phosphorylation state of the control point, T305/T306.

}, keywords = {Amino Acid Sequence, Animals, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Excitatory Postsynaptic Potentials, Hippocampus, Holoenzymes, In Vitro Techniques, Long-Term Potentiation, Long-Term Synaptic Depression, Mutation, Neurons, Patch-Clamp Techniques, Phosphorylation, Synapses, Time Factors, Transfection}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.0133-10.2010}, author = {Pi, Hyun Jae and Otmakhov, Nikolai and Lemelin, David and Paul De Koninck and Lisman, John} } @article {746, title = {CaMKII control of spine size and synaptic strength: role of phosphorylation states and nonenzymatic action.}, journal = {Proc Natl Acad Sci U S A}, volume = {107}, year = {2010}, month = {2010 Aug 10}, pages = {14437-42}, abstract = {

CaMKII is an abundant synaptic protein strongly implicated in plasticity. Overexpression of autonomous (T286D) CaMKII in CA1 hippocampal cells enhances synaptic strength if T305/T306 sites are not phosphorylated, but decreases synaptic strength if they are phosphorylated. It has generally been thought that spine size and synaptic strength covary; however, the ability of CaMKII and its various phosphorylation states to control spine size has not been previously examined. Using a unique method that allows the effects of overexpressed protein to be monitored over time, we found that all autonomous forms of CaMKII increase spine size. Thus, for instance, the T286D/T305D/T306D form increases spine size but decreases synaptic strength. Further evidence for such dissociation is provided by experiments with the T286D form that has been made catalytically dead. This form fails to enhance synaptic strength but increases spine size, presumably by a structural process. Thus very different mechanisms govern how CaMKII affects spine structure and synaptic function.

}, keywords = {Animals, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Dendritic Spines, Electrophysiology, Hippocampus, Microscopy, Confocal, Neuronal Plasticity, Phosphorylation, Rats, Rats, Sprague-Dawley, Synapses}, issn = {1091-6490}, doi = {10.1073/pnas.1009268107}, author = {Pi, Hyun Jae and Otmakhov, Nikolai and El Gaamouch, Farida and Lemelin, David and Paul De Koninck and Lisman, John} }