Nature Neuroscience
2, 331 - 338 (1999)
doi:10.1038/7243
G-protein-coupled receptors act via protein kinase C and Src to regulate
NMDA receptorsW-Y. Lu1, Z-G. Xiong1, S. Lei1, B. A. Orser2, E. Dudek3, M. D. Browning3
& J. F. MacDonald11
Departments of Physiology, Pharmacology, University of Toronto, Toronto M5S 1A8, Canada
2
Department of Anaesthesia, University of Toronto, Toronto M5S 1A8, Canada
3
Department of Pharmacology, Program in Neuroscience, University of Colorado Health Science Center, University of Colorado, Denver, Colorado 80262, USA
Correspondence should be addressed to J. F. MacDonald j.macdonald@utoronto.caThe N-methyl-D-aspartate (NMDA) receptor contributes to synaptic
plasticity in the central nervous system and is both serine-threonine and
tyrosine phosphorylated. In CA1 pyramidal neurons of the hippocampus, activators
of protein kinase C (PKC) as well as the G-protein-coupled receptor ligands
muscarine and lysophosphatidic acid enhanced NMDA-evoked currents. Unexpectedly,
this effect was blocked by inhibitors of tyrosine kinases, including a Src
required sequence and an antibody selective for Src itself. In neurons from
mice lacking c-Src, PKC-dependent upregulation was absent. Thus, G-protein-coupled
receptors can regulate NMDA receptor function indirectly through a PKC-dependent
activation of the non-receptor tyrosine kinase (Src) signaling cascade.
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