NMDA Channel Regulation by Channel-Associated Protein Tyrosine Kinase Src

@article{Yu1997NMDACR,
  title={NMDA Channel Regulation by Channel-Associated Protein Tyrosine Kinase Src},
  author={X M Yu and Rand Askalan and G J Keil and Michael W. Salter},
  journal={Science},
  year={1997},
  volume={275},
  pages={674 - 678}
}
The N-methyl-D-aspartate (NMDA) receptor mediates synaptic transmission and plasticity in the central nervous system (CNS) and is regulated by tyrosine phosphorylation. In membrane patches excised from mammalian central neurons, the endogenous tyrosine kinase Src was shown to regulate the activity of NMDA channels. The action of Src required a sequence [Src(40–58)] within the noncatalytic, unique domain of Src. In addition, Src coprecipitated with NMDA receptor proteins. Finally, endogenous Src… 
View on AAAS
ncbi.nlm.nih.gov
622 Citations
Highly Influential Citations
16
Background Citations
172
Methods Citations
13
Results Citations
5

622 Citations

Citation Type

Citation Type

G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA receptors
TLDR
G-protein-coupled receptors can regulate NMDA receptor function indirectly through a PKC-dependent activation of the non-receptor tyrosine kinase (Src) signaling cascade.
Src kinases: a hub for NMDA receptor regulation
TLDR
In the central nervous system, synaptic strength is regulated partly by changes in the function and number of postsynaptic glutamate receptors, and members of the Src family of protein tyrosine kinases upregulate NMDAR function, thereby gating the production of N MDAR-dependent synaptic potentiation.
Regulation of NMDA receptors by cyclin-dependent kinase-5
TLDR
It is demonstrated that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells, suggesting that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs.
NMDA receptor regulation by Src kinase signalling in excitatory synaptic transmission and plasticity
Src, N-methyl-D-aspartate (NMDA) receptors, and synaptic plasticity.
  • M. Salter
  • Biology
    Biochemical pharmacology
  • 1998
NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1
TLDR
It is found that RACK1 binds both the NR2B subunit of the NMDA receptor and the nonreceptor protein tyrosine kinase, Fyn and may play a role in synaptic plasticity, addiction, learning, and memory.
Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition
TLDR
Evidence is presented that Src potentiates NMDA-receptor currents by reducing the tonic inhibition of receptors composed of NR1 and NR2A subunits by extracellular zinc and that three C-terminal tyrosine residues ofNR2A are required for Src's modulation of the zinc sensitivity of NMDA receptors.
Post-synaptic density-93 mediates tyrosine-phosphorylation of the N-methyl-d-aspartate receptors
Src, a molecular switch governing gain control of synaptic transmission mediated by N-methyl-D-aspartate receptors.
  • X. Yu, M. Salter
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
TLDR
It is proposed that the boost in NMDA receptor function produced by the coincidence of activating Src and raising intracellular sodium may be important in physiological and pathophysiological enhancement of excitatory transmission in the dorsal horn of the spinal cord and elsewhere in the central nervous system.
Modulation of NMDA receptors.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 29 REFERENCES
Regulation of NMDA receptors by tyrosine kinases and phosphatases
TLDR
Evidence is presented that in mammalian central neurons tyrosine phosphorylation regulates the function of the NMDA (N-methyl-D-aspartate) receptor, a subtype of excitatory amino-acid receptor, which may be important in neuronal development, plasticity and toxicity.
Inactivation of NMDA Receptors by Direct Interaction of Calmodulin with the NR1 Subunit
Ca(2+)-independent reduction of N-methyl-D-aspartate channel activity by protein tyrosine phosphatase.
TLDR
Results indicate that NMDA channel activity is reduced by a protein tyrosine phosphatase associated with the channel complex, and this decline is not dependent upon Ca2+.
Differential Tyrosine Phosphorylation of N-Methyl-D-aspartate Receptor Subunits (*)
TLDR
Immunocytochemical staining with an anti-phosphotyrosine antibody demonstrates that there are high levels of phosphotYrosine, which co-localizes with glutamate receptors at excitatory synapses on cultured hippocampal neurons and suggests that tyrosine phosphorylation of the NR2 subunits may be important for regulating NMDA receptor function.
Subtype‐specific regulation of recombinant NMDA receptor‐channels by protein tyrosine kinases of the src family.
TLDR
In a mutant channel consisting of NR1 and a C‐terminal deletion mutant of NR2A (NR2A delta C), src and fyn kinases lost their potentiating effects indicating that the phosphorylation of tyrosine(s) in the C-terminal domain of NR 2A affects the current flux through native NMDA receptor‐channels.
Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95.
TLDR
The yeast two-hybrid system was used to show that the cytoplasmic tails of NMDA receptor subunits interact with a prominent postsynaptic density protein PSD-95, which may affect the plasticity of excitatory synapses.
Regulation of NMDA channel function by endogenous Ca2+-dependent phosphatase
TLDR
In adult neurons, calcineurin, activated by calcium entry through native NMDA channels, shortens the duration of channel openings, which is consistent with the importance of phosphorylation of the NMDA-receptor complex in the short- and long-term control of neuronal excitability.
Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation
THE roles of N-methyl-D-aspartate (NMDA) receptors and protein kinase C (PKC) are critical in generating and maintaining a variety of sustained neuronal responses. In the nociceptive (pain-sensing)…
The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B.
TLDR
The findings suggest that, in the forebrain, NMDA receptor subunit 2B may serve to anchor NMDA receptors at the postsynaptic membrane through its interaction with the PSD, and the prominent presence of tyrosine phosphate further suggests that theNMDA receptor may be regulated by tyrosinesine phosphorylation or that it may participate in signaling through tyrosin phosphorylated and through its ion channel.
Changing subunit composition of heteromeric NMDA receptors during development of rat cortex
TLDR
Direct evidence is presented that NMDA receptors exist in rat neocortex as heteromeric complexes of considerable heterogeneity, some containing both NR2A and NR2B subunits.
...
1
2
3
...