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Current Drug Targets
ISSN (Print): 1389-4501
ISSN (Online): 1873-5592
DOI: 10.2174/1389450013348452      Price:  $58

Convergence of PKC-Dependent Kinase Signal Cascades on NMDA Receptors

Author(s): J. F. Macdonald, S. A. Kotecha, W. Y. Lu and M. F. Jackson
Pages 299-312 (14)
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 CAK beta / Src tyrosine kinase cascade, enhances NMDAR activation and may increase the number of receptors expressed in synapses. In contras t, direct phosphorylation of NMDARs by PKC increases the sensitivity of NMDA channel inactivation to intracellular Ca2+. In CA1 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.
PKC-Dependent Kinase Signal, NMDARs, C-terminus cassettes, NMDAR-mediated current, CA1 pyramidal neurons
Canadian Institutes of Health Research Group The Synapse, Departments of Physiology&Pharmacology, University of Toronto, Canada