Control of Excitatory Synaptic Transmission by C-terminal Src Kinase

The induction of long-term potentiation at CA3-CA1 synapses is caused by an N-methyl-d-aspartate (NMDA) receptordependent accumulation of intracellular Ca2+, followed by Src family kinase activation and a positive feedback enhancement of NMDA receptors (NMDARs). Nevertheless, the amplitude of baseli...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2008-06, Vol.283 (25), p.17503-17514
Main Authors: Xu, Jindong, Weerapura, Manjula, Ali, Mohammad K., Jackson, Michael F., Li, Hongbin, Lei, Gang, Xue, Sheng, Kwan, Chun L., Manolson, Morris F., Yang, Kai, MacDonald, John F., Yu, Xian-Min
Format: Article
Language:English
Subjects:
Animals
Brain - metabolism
Chlorocebus aethiops
COS Cells
CSK Tyrosine-Protein Kinase
Dendrites - metabolism
Hippocampus - metabolism
Humans
Long-Term Potentiation
Models, Biological
Neurons - metabolism
Protein-Tyrosine Kinases - metabolism
Signal Transduction
src-Family Kinases - metabolism
Subcellular Fractions
Synaptic Transmission
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The induction of long-term potentiation at CA3-CA1 synapses is caused by an N-methyl-d-aspartate (NMDA) receptordependent 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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M800917200