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Published in: Journal of Computational Neuroscience 3/2009

01-12-2009

Dissecting cooperative calmodulin binding to CaM kinase II: a detailed stochastic model

Authors: Michael J. Byrne, John A. Putkey, M. Neal Waxham, Yoshihisa Kubota

Published in: Journal of Computational Neuroscience | Issue 3/2009

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Abstract

Calmodulin (CaM) is a major Ca2+ binding protein involved in two opposing processes of synaptic plasticity of CA1 pyramidal neurons: long-term potentiation (LTP) and depression (LTD). The N- and C-terminal lobes of CaM bind to its target separately but cooperatively and introduce complex dynamics that cannot be well understood by experimental measurement. Using a detailed stochastic model constructed upon experimental data, we have studied the interaction between CaM and Ca2+-CaM-dependent protein kinase II (CaMKII), a key enzyme underlying LTP. The model suggests that the accelerated binding of one lobe of CaM to CaMKII, when the opposing lobe is already bound to CaMKII, is a critical determinant of the cooperative interaction between Ca2+, CaM, and CaMKII. The model indicates that the target-bound Ca2+ free N-lobe has an extended lifetime and may regulate the Ca2+ response of CaMKII during LTP induction. The model also reveals multiple kinetic pathways which have not been previously predicted for CaM-dissociation from CaMKII.

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Appendix
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Metadata
Title
Dissecting cooperative calmodulin binding to CaM kinase II: a detailed stochastic model
Authors
Michael J. Byrne
John A. Putkey
M. Neal Waxham
Yoshihisa Kubota
Publication date
01-12-2009
Publisher
Springer US
Published in
Journal of Computational Neuroscience / Issue 3/2009
Print ISSN: 0929-5313
Electronic ISSN: 1573-6873
DOI
https://doi.org/10.1007/s10827-009-0173-3

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