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Neurogranin enhances synaptic strength through its interaction with calmodulin

Learning-correlated plasticity at CA1 hippocampal excitatory synapses is dependent on neuronal activity and NMDA receptor (NMDAR) activation. However, the molecular mechanisms that transduce plasticity stimuli to postsynaptic potentiation are poorly understood. Here, we report that neurogranin (Ng),...

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Detalles Bibliográficos
Autores principales: Zhong, Ling, Cherry, Tiffani, Bies, Christine E, Florence, Matthew A, Gerges, Nashaat Z
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736013/
https://www.ncbi.nlm.nih.gov/pubmed/19713936
http://dx.doi.org/10.1038/emboj.2009.236
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author Zhong, Ling
Cherry, Tiffani
Bies, Christine E
Florence, Matthew A
Gerges, Nashaat Z
author_facet Zhong, Ling
Cherry, Tiffani
Bies, Christine E
Florence, Matthew A
Gerges, Nashaat Z
author_sort Zhong, Ling
collection PubMed
description Learning-correlated plasticity at CA1 hippocampal excitatory synapses is dependent on neuronal activity and NMDA receptor (NMDAR) activation. However, the molecular mechanisms that transduce plasticity stimuli to postsynaptic potentiation are poorly understood. Here, we report that neurogranin (Ng), a neuron-specific and postsynaptic protein, enhances postsynaptic sensitivity and increases synaptic strength in an activity- and NMDAR-dependent manner. In addition, Ng-mediated potentiation of synaptic transmission mimics and occludes long-term potentiation (LTP). Expression of Ng mutants that lack the ability to bind to, or dissociate from, calmodulin (CaM) fails to potentiate synaptic transmission, strongly suggesting that regulated Ng–CaM binding is necessary for Ng-mediated potentiation. Moreover, knocking-down Ng blocked LTP induction. Thus, Ng–CaM interaction can provide a mechanistic link between induction and expression of postsynaptic potentiation.
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spelling pubmed-27360132009-09-01 Neurogranin enhances synaptic strength through its interaction with calmodulin Zhong, Ling Cherry, Tiffani Bies, Christine E Florence, Matthew A Gerges, Nashaat Z EMBO J Article Learning-correlated plasticity at CA1 hippocampal excitatory synapses is dependent on neuronal activity and NMDA receptor (NMDAR) activation. However, the molecular mechanisms that transduce plasticity stimuli to postsynaptic potentiation are poorly understood. Here, we report that neurogranin (Ng), a neuron-specific and postsynaptic protein, enhances postsynaptic sensitivity and increases synaptic strength in an activity- and NMDAR-dependent manner. In addition, Ng-mediated potentiation of synaptic transmission mimics and occludes long-term potentiation (LTP). Expression of Ng mutants that lack the ability to bind to, or dissociate from, calmodulin (CaM) fails to potentiate synaptic transmission, strongly suggesting that regulated Ng–CaM binding is necessary for Ng-mediated potentiation. Moreover, knocking-down Ng blocked LTP induction. Thus, Ng–CaM interaction can provide a mechanistic link between induction and expression of postsynaptic potentiation. Nature Publishing Group 2009-10-07 2009-08-27 /pmc/articles/PMC2736013/ /pubmed/19713936 http://dx.doi.org/10.1038/emboj.2009.236 Text en Copyright © 2009, European Molecular Biology Organization http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.
spellingShingle Article
Zhong, Ling
Cherry, Tiffani
Bies, Christine E
Florence, Matthew A
Gerges, Nashaat Z
Neurogranin enhances synaptic strength through its interaction with calmodulin
title Neurogranin enhances synaptic strength through its interaction with calmodulin
title_full Neurogranin enhances synaptic strength through its interaction with calmodulin
title_fullStr Neurogranin enhances synaptic strength through its interaction with calmodulin
title_full_unstemmed Neurogranin enhances synaptic strength through its interaction with calmodulin
title_short Neurogranin enhances synaptic strength through its interaction with calmodulin
title_sort neurogranin enhances synaptic strength through its interaction with calmodulin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736013/
https://www.ncbi.nlm.nih.gov/pubmed/19713936
http://dx.doi.org/10.1038/emboj.2009.236
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