Involvement of Neurogranin in the Modulation of Calcium/Calmodulin-Dependent Protein Kinase II, Synaptic Plasticity, and Spatial Learning: A Study with Knockout Mice

Neurogranin/RC3 is a neural-specific Ca2+-sensitive calmodulin (CaM)-binding protein whose CaM-binding affinity is modulated by phosphorylation and oxidation. Here we show that deletion of the Ng gene in mice did not result in obvious developmental or neuroanatomical abnormalities but caused an impa...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2000-10, Vol.97 (21), p.11232-11237
Main Authors: Pak, Jhang Ho, Huang, Freesia L., Li, Junfa, Balschun, Detlef, Reymann, Klaus G., Chiang, Chin, Westphal, Heiner, Huang, Kuo-Ping
Format: Article
Language:English
Subjects:
ANg gene
Animals
Antibodies
Base Sequence
Biochemistry
Biological Sciences
Calcium
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Calmodulin-Binding Proteins - genetics
Calmodulin-Binding Proteins - physiology
DNA Primers
Female
Genotypes
Hippocampus
In Vitro Techniques
Learning - physiology
Long term potentiation
Male
Mazes
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - physiology
Neurogranin
Neuronal Plasticity
Neurons
Ng gene
Oxidation
Phosphorylation
Proteins
Quadrants
Rodents
Signal Transduction
sodium nitroprusside
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Summary:Neurogranin/RC3 is a neural-specific Ca2+-sensitive calmodulin (CaM)-binding protein whose CaM-binding affinity is modulated by phosphorylation and oxidation. Here we show that deletion of the Ng gene in mice did not result in obvious developmental or neuroanatomical abnormalities but caused an impairment of spatial learning and changes in hippocampal short- and long-term plasticity (paired-pulse depression, synaptic fatigue, long-term potentiation induction). These deficits were accompanied by a decreased basal level of the activated Ca2+/CaM-dependent kinase II (CaMKII)(≈ 60% of wild type). Furthermore, hippocampal slices of the mutant mice displayed a reduced ability to generate activated CaMKII after stimulation of protein phosphorylation and oxidation by treatments with okadaic acid and sodium nitroprusside, respectively. These results indicate a central role of Ng in the regulation of CaMKII activity with decisive influences on synaptic plasticity and spatial learning.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.210184697