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PMID: 19713936 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Neurogranin enhances synaptic strength through its interaction with calmodulin.

The EMBO journal ·Vol. 28 ·No. 19 ·2009-10-07 ·Pages 3027-39

Zhong L, Cherry T, Bies CE, Florence MA, Gerges NZ

Abstract

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.

MeSH Terms
Animals Calcium/metabolism Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism Calmodulin/genetics,metabolism Cells, Cultured Gene Expression Hippocampus/cytology Long-Term Potentiation Neurogranin/analysis,genetics,metabolism Neuronal Plasticity Neurons/cytology Protein Binding Rats Receptors, AMPA/metabolism Receptors, N-Methyl-D-Aspartate/metabolism Spine/ultrastructure Synaptic Transmission
Chemicals
Calmodulin Receptors, AMPA Receptors, N-Methyl-D-Aspartate Neurogranin Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium glutamate receptor ionotropic, AMPA 1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zhong Ling
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226 0509, USA.
Cherry Tiffani
Bies Christine E
Florence Matthew A
Gerges Nashaat Z
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/emboj.2009.236
Published
2009-10-07
Epub
2009-00-27
Pages
3027-39
Language
English
Region
England
NLM ID
8208664
PMCID
PMC2736013
Subset
IM
Grants
NIA NIH HHS · R01 AG032320 · United States
NIA NIH HHS · AG032320 · United States
Corrections
CommentIn
PMID: 19809472
External Links
PubMed source DOI: 10.1038/emboj.2009.236 PMC Full Text View journal details
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