References
Query Results -- Details
MGI Accession ID: MGI:3761918
J Number: J:126729
Other Accession IDs:
Title: Participation of NMDA-mediated phosphorylation and oxidation of neurogranin in the regulation of Ca2+- and Ca2+/calmodulin-dependent neuronal signaling in the hippocampus.
Authors: Wu J; Huang KP; Huang FL
Journal: J Neurochem
Volume: 86
Issue: 6
Date: 2003 Sep
Year: 2003
Pages: 1524-33
Review Status: Peer Reviewed
Abstract:
Neurogranin/RC3 (Ng) is a postsynaptic protein kinase C (PKC) substrate and calmodulin (CaM)-binding protein whose CaM-binding affinity is modulated by Ca2+, phosphorylation and oxidation. Ng has been implicated in the modulation of postsynaptic signal transduction pathways and synaptic plasticity. Previously, we showed a severe deficit of spatial memory in Ng knockout (KO) mice. Activation of the NMDA receptor and its downstream signaling molecules are known to be involved in long-term memory formation. In the present study, using mouse hippocampal slices, we demonstrated that NMDA induced a rapid and transient phosphorylation and oxidation of Ng. NMDA also caused activation of PKC as evidenced by their phosphorylations, whereas, such activations were greatly reduced in the KO mice. A higher degree of phosphorylation of Ca2+/CaM-dependent kinase II and activation of cyclic AMP-dependent protein kinase were also evident in the WT compared to those of the KO mice. Phosphorylation of downstream targets, including mitogen-activated protein kinases and cAMP response element-binding protein, were significantly attenuated in the KO mice. These results suggest that by its Ca2+-sensitive CaM-binding feature, and through its phosphorylation and oxidation, Ng regulates the Ca2+- and Ca2+/CaM-dependent signaling pathways subsequent to the stimulation of NMDA receptor. These findings support the hypothesis that the derangement of hippocampal signal transduction cascades in Ng KO mice causes the deficits in synaptic plasticity, learning and memory that occur in these mice.
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