Control of excitatory synaptic transmission by C-terminal Src kinase
Abstract
The induction of long-term potentiation at CA3-CA1 synapses is caused by an N-methyl-D-aspartate (NMDA) receptor-dependent accumulation of intracellular Ca2+, followed by Src family kinase activation and a positive feedback enhancement of NMDA receptors (NMDARs). Nevertheless, the amplitude of baseline transmission remains remarkably constant even though low frequency stimulation is also associated with an NMDAR-dependent influx of Ca2+ into dendritic spines. We show here that an interaction between C-terminal Src kinase (Csk) and NMDARs controls the Src-dependent regulation of NMDAR activity. Csk associates with the NMDAR signaling complex in the adult brain, inhibiting the Src-dependent potentiation of NMDARs in CA1 neurons and attenuating the Src-dependent induction of long-term potentiation. Csk associates directly with Src-phosphorylated NR2 subunits in vitro. An inhibitory antibody for Csk disrupts this physical association, potentiates NMDAR mediated excitatory postsynaptic currents, and induces long-term potentiation at CA3-CA1 synapses. Thus, Csk serves to maintain the constancy of baseline excitatory synaptic transmission by inhibiting Src kinase-dependent synaptic plasticity in the hippocampus. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
Publication Title
Journal of Biological Chemistry
Recommended Citation
Xu, J., Weerapura, M., Ali, M., Jackson, M., Li, H., Lei, G., Xue, S., & Kwan, C. (2008). Control of excitatory synaptic transmission by C-terminal Src kinase. Journal of Biological Chemistry (25), 17503-17514. https://doi.org/10.1074/jbc.M800917200
