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), 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.
Zhong
Ling
L
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226 0509, USA.
Cherry
Tiffani
T
Bies
Christine E
CE
Florence
Matthew A
MA
Gerges
Nashaat Z
NZ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology; D017774:Long-Term Potentiation; D051579:Neurogranin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology*; D011485:Protein Binding; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013131:Spine / Q000648:ultrastructure; D009435:Synaptic Transmission
D002118:Calcium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002147:Calmodulin; D051579:Neurogranin; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate