Journal
JOURNAL OF COMPUTATIONAL NEUROSCIENCE
Volume 27, Issue 3, Pages 621-638Publisher
SPRINGER
DOI: 10.1007/s10827-009-0173-3
Keywords
Calmodulin; CaMKII; Synaptic plasticity; Gillespie algorithm; Particle swarm theory
Funding
- NIGMS NIH HHS [GM069611, R01 GM069611] Funding Source: Medline
- NINDS NIH HHS [P01 NS038310, T32 NS041226, NS 041226, R01 NS026086, NS26086, R56 NS026086, NS038310] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available