Subunit exchange enhances information retention by CaMKII in dendritic spines

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Abstract

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.

Data availability

The model and the instructions to generate data analysed in this study are available at https://github.com/dilawar/SinghAndBhalla_CaMKII_SubunitExchange_2018 .

Article and author information

Author details

Dilawar Singh

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-4645-3211
Upinder Singh Bhalla

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India

For correspondence
bhalla@ncbs.res.in

Competing interests
Upinder Singh Bhalla, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0003-1722-5188

Funding

Science and Engineering Research Board (JC Bose Fellowship #SB/S2/JCB-023/2016)

Upinder Singh Bhalla

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.