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Kinase activity is not required for αCaMKII-dependent presynaptic plasticity at CA3-CA1 synapses

Abstract

Using targeted mouse mutants and pharmacologic inhibition of αCaMKII, we demonstrate that the αCaMKII protein, but not its activation, autophosphorylation or its ability to phosphorylate synapsin I, is required for normal short-term presynaptic plasticity. Furthermore, αCaMKII regulates the number of docked vesicles independent of its ability to be activated. These results indicate that αCaMKII has a nonenzymatic role in short-term presynaptic plasticity at hippocampal CA3-CA1 synapses.

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Figure 1: Phosphorylation of synapsin I and CaMKII-T286/T287 in synaptosomes obtained from αCaMKII mutants.
Figure 2: Presynaptic short-term plasticity requires αCaMKII protein, but not its autophosphorylation, activation or activity.
Figure 3: αCaMKII protein regulates the number of docked vesicles.

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Acknowledgements

We greatly appreciate the help of H. Beck, M. Merkens, R. Anwyl, K. Wang and R. Colbran for their (hands-on) advice on the use of CaMKII inhibitors, and from G. Borst and S. Kushner and members of the Silva and Elgersma lab for stimulating discussions and critically reading the manuscript. We thank M. Elgersma, H. van der Burg and E. Phillips for technical support. This work was supported by grants from NWO-ZonMW (TOP, VIDI) and Neuro-BSIK to Y.E. We also thank the University of Alabama, Birmingham Neuroscience Cores (P30-NS47466, P30-HD38985, P30-NS57098).

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Correspondence to Ype Elgersma.

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Hojjati, M., van Woerden, G., Tyler, W. et al. Kinase activity is not required for αCaMKII-dependent presynaptic plasticity at CA3-CA1 synapses. Nat Neurosci 10, 1125–1127 (2007). https://doi.org/10.1038/nn1946

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