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Molecular memory by reversible translocation of calcium/calmodulin-dependent protein kinase II

Abstract

Synaptic plasticity is thought to be a key process for learning, memory and other cognitive functions of the nervous system. The initial events of plasticity require the conversion of brief electrical signals into alterations of the biochemical properties of synapses that last for much longer than the initial stimuli. Here we show that a regulator of synaptic plasticity, calcium/calmodulin-dependent protein kinase IIα (CaMKII), sequentially translocates to postsynaptic sites, undergoes autophosphorylation and gets trapped for several minutes until its dissociation is induced by secondary autophosphorylation and phosphatase 1 action. Once dissociated, CaMKII shows facilitated translocation for several minutes. This suggests that trapping of CaMKII by its targets and priming of CaMKII translocation may function as biochemical memory mechanisms that change the signaling capacity of synapses.

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Figure 1: Field stimulation induces a synaptically trapped state of CaMKII.
Figure 2: Absence of a trapped state of CaMKII in a Thr286 mutant of CaMKII.
Figure 3: Transition from a rapidly reversible state to a synaptically trapped state of CaMKII by increased amplitude of local glutamate stimuli.
Figure 4: The duration of the trapped state of CaMKII is regulated by reversible autophosphorylation at Thr286 and Thr305/Thr306.
Figure 5: Identification of a cytosolic state of CaMKII primed for synaptic translocation.
Figure 6: Control measurements showing the same translocation analysis using neurons transfected with the autophosphorylation-deficient mutant GFP–CaMKII (Thr286Ala).

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Acknowledgements

We thank G. Augustine, L. Katz, A. Means and C. Fink, Duke University, for comments. This work was supported by grant RO1-GM48113 from the National Institute of General Medicine.

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Correspondence to T. Meyer.

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Shen, K., Teruel, M., Connor, J. et al. Molecular memory by reversible translocation of calcium/calmodulin-dependent protein kinase II. Nat Neurosci 3, 881–886 (2000). https://doi.org/10.1038/78783

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