Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases

@inproceedings{Niethammer1996InteractionBT,
  title={Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases},
  author={Martin Niethammer and E. Kim and Morgan Sheng},
  booktitle={The Journal of neuroscience : the official journal of the Society for Neuroscience},
  year={1996}
}
Selective concentration and anchoring of ionotropic receptors at the synapse is essential for neuronal signaling. Little is known about the molecules that mediate receptor clustering in the CNS. With use of the yeast two-hybrid system to screen a rat brain cDNA library and by in vitro binding assays, we have identified an interaction between NMDA receptor subunits 2A and 2B (NR2A and NR2B) and three distinct members of the PSD-95/SAP90 family of membrane-associated putative guanylate kinases… 

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References

SHOWING 1-10 OF 66 REFERENCES
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.
Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases
TLDR
Functional and biochemical evidence is presented that cell-surface clustering of Shaker-subfamily K+ channels is mediated by the PSD-95 family of membrane-associated putative guanylate kinases, and the ability of PDZ domains to function as independent modules for protein–protein interaction, and their presence in other junction-associated molecules suggest that PDZ-domain-containing polypeptides may be widely involved in the organization of proteins at sites of membrane specialization.
Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits.
Heteromeric NMDA Receptors: Molecular and Functional Distinction of Subtypes
TLDR
Molecular cloning identified three complementary DNA species of rat brain, encoding NMDA receptor subunits NMDAR2A (NR2A), NR2B, and NR2C, which are 55 to 70% ientical in sequence, and these are structurally related, with less than 20% sequence identity, to other excitatory amino acid receptor sub Units.
Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein
TLDR
Light and immunoelectron microscopic analysis of the rat hippocampal formation revealed that SAP97 is localized in the presynaptic nerve termini of excitatory synapses, suggesting that members of the SAP90/SAP97 subfamily may be involved in the site specific assembly, stability or functions of membrane specialization at sites of cell-cell contact.
Transmembrane topology of two kainate receptor subunits revealed by N-glycosylation.
  • Z. Wo, R. Oswald
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1994
TLDR
It is shown that a portion of these receptors previously thought to be a large intracellular loop is actually located extracellularly and an alternative model for the transmembrane topology of kainate receptors is proposed that could potentially serve as a framework for future detailed study of the structure of this important class of neurotransmitter receptors.
Regulation of ion channel distribution at synapses.
TLDR
It is reasonable to expect that the basic mechanisms currently being elucidated at the neuromuscular junction will lead to greater understanding of how the CNS uses ion channel distribution to modulate synaptic activity.
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.
Mammalian ionotropic glutamate receptors
...
...