Autonomous CaMKII can promote either long-term potentiation or long-term depression, depending on the state of T305/T306 phosphorylation

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 d...

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Bibliographic Details
Published in:The Journal of neuroscience 2010-06, Vol.30 (26), p.8704-8709
Main Authors: Pi, Hyun Jae, Otmakhov, Nikolai, Lemelin, David, De Koninck, Paul, Lisman, John
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Brief Communications
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
Excitatory Postsynaptic Potentials - drug effects
Excitatory Postsynaptic Potentials - physiology
Hippocampus - drug effects
Hippocampus - physiology
Holoenzymes - genetics
Holoenzymes - metabolism
In Vitro Techniques
Long-Term Potentiation - drug effects
Long-Term Potentiation - physiology
Long-Term Synaptic Depression - drug effects
Long-Term Synaptic Depression - physiology
Mutation
Neurons - drug effects
Neurons - physiology
Patch-Clamp Techniques
Phosphorylation
Synapses - drug effects
Synapses - physiology
Time Factors
Transfection
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.0133-10.2010