Convergence of PKC-dependent kinase signal cascades on NMDA receptors.
Synaptic plasticity, or long-term potentiation (LTP), of excitatory synapses in the hippocampus contributes to learning and the establishment of spatial memories. In the CA1 region, induction of LTP enhances the function of postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) because of the Ca2+-calmodulin kinase II (CaMKII)-dependent phosphorylation of this subtype of glutamate receptor. Entry of Ca2+, via N-methyl-D-aspartate receptors (NMDARs), during strong synaptic stimulation provides the stimulus to trigger phosphorylation of AMPARs. However, this induction also requires activation of a protein kinase C (PKC)-dependent tyrosine kinase signal cascade and a concomitant upregulation of NMDARs. This review focuses upon NMDARs as potential targets of PKC and/or of the PKC-dependent tyrosine kinase cascade. PKC, acting via the CAKbeta/Src tyrosine kinase cascade, enhances NMDAR activation and may increase the number of receptors expressed in synapses. In contrast, direct phosphorylation of NMDARs by PKC increases the sensitivity of NMDA channel inactivation to intracellular Ca2+. In CAI neurons, PKC provides a point of convergence of control of NMDARs and synaptic plasticity for a wide variety of G-protein coupled and growth factor receptors.
MacDonald
J F
JF
Canadian Institutes of Health Research Group, The Synapse, Department of Physiology, University of Toronto, Canada.
Kotecha
S A
SA
Lu
W Y
WY
Jackson
M F
MF
D000818:Animals; D018846:Excitatory Amino Acids / Q000502:physiology; D006801:Humans; D009473:Neuronal Plasticity; D011493:Protein Kinase C / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology
D018846:Excitatory Amino Acids; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D011493:Protein Kinase C