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Subunit exchange enhances information retention by CaMKII in dendritic spines

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 stat...

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Autores principales: Singh, Dilawar, Bhalla, Upinder Singh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286124/
https://www.ncbi.nlm.nih.gov/pubmed/30418153
http://dx.doi.org/10.7554/eLife.41412
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author Singh, Dilawar
Bhalla, Upinder Singh
author_facet Singh, Dilawar
Bhalla, Upinder Singh
author_sort Singh, Dilawar
collection PubMed
description 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.
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spelling pubmed-62861242018-12-11 Subunit exchange enhances information retention by CaMKII in dendritic spines Singh, Dilawar Bhalla, Upinder Singh eLife Computational and Systems Biology 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. eLife Sciences Publications, Ltd 2018-11-12 /pmc/articles/PMC6286124/ /pubmed/30418153 http://dx.doi.org/10.7554/eLife.41412 Text en © 2018, Singh and Bhalla http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Singh, Dilawar
Bhalla, Upinder Singh
Subunit exchange enhances information retention by CaMKII in dendritic spines
title Subunit exchange enhances information retention by CaMKII in dendritic spines
title_full Subunit exchange enhances information retention by CaMKII in dendritic spines
title_fullStr Subunit exchange enhances information retention by CaMKII in dendritic spines
title_full_unstemmed Subunit exchange enhances information retention by CaMKII in dendritic spines
title_short Subunit exchange enhances information retention by CaMKII in dendritic spines
title_sort subunit exchange enhances information retention by camkii in dendritic spines
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286124/
https://www.ncbi.nlm.nih.gov/pubmed/30418153
http://dx.doi.org/10.7554/eLife.41412
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