Molecular bistables are strong candidates for long-term information storage, for example, in synaptic plasticity. Calcium/calmodulin dependent protein Kinase II (CaMKII) is a highly expressed synaptic protein which has been proposed to form a molecular bistable switch capable of maintaining its state for years despite protein turnover and stochastic noise. It has recently been shown that CaMKII holoenzymes exchange subunits among themselves. Here we used computational methods to analyze the effect of subunit exchange on the CaMKII pathway in the presence of diffusion in two different micro-environments, the post synaptic density (PSD) and spine cytosol. We show that CaMKII exhibits multiple timescales of activity due to subunit exchange. Further, subunit exchange enhances information retention by CaMKII both by improving the stability of its switching in the PSD, and by slowing the decay of its activity in the spine cytosol. The existence of diverse timescales in the synapse has important theoretical implications for memory storage in networks.
The model and the instructions to generate data analysed in this study are available at https://github.com/dilawar/SinghAndBhalla_CaMKII_SubunitExchange_2018 .
- Upinder Singh Bhalla
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Leslie C Griffith, Brandeis University, United States
© 2018, Singh & Bhalla
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