PMID- 15802183
OWN - NLM
STAT- MEDLINE
DCOM- 20050705
LR  - 20171116
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 132
IP  - 2
DP  - 2005
TI  - The NR1-4 C-terminus interferes with N-methyl-D-aspartate receptor-mediated 
      excitotoxicity: evidence against a typical T/SXV-PDZ interaction.
PG  - 281-98
AB  - The N-methyl-D-aspartate receptor (NMDAR) plays a key role in the neural 
      plasticity that underlies learning and memory in vivo. The plasticity exhibited 
      by NMDARs may also contribute to disease pathogenesis, as a number of disorders 
      are caused or exacerbated by exaggerated NMDAR activity. The NMDAR is composed of 
      two obligatory types of subunits, NR1 and NR2. These transmembrane proteins 
      include large intracellular C-termini that have yet to be fully characterized. We 
      have developed a three-color fluorescence system in order to visualize NMDAR 
      expression in living cells. Using excitotoxicity as a proxy for exaggerated NMDAR 
      activity, we analyzed the effect of over-expressing NR1-4 and NR2A C-terminal 
      domains on exaggerated NMDAR function. We demonstrate that a determinant within 
      the C-terminal domain of NR1-4 (C02') is important for NMDAR excitotoxicity, 
      whereas no novel determinants were identified in the NR2A C-terminus. Through the 
      use of heterologous cells, and by examining the interaction between the 
      prototypical NMDAR-binding partner postsynaptic density-95 (PSD-95), we show that 
      this effect is unlikely to be mediated through a classical interaction with 
      PSD-95.
FAU - Mattar, P A
AU  - Mattar PA
AD  - The BioTherapeutics Research Group, Robarts Research Institute, P.O. Box 5015, 
      100 Perth Drive, London, Ontario, Canada N6A 5K8.
FAU - Holmes, K D
AU  - Holmes KD
FAU - Dekaban, G A
AU  - Dekaban GA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, rat)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurotoxins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (postsynaptic density proteins)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Animals
MH  - Blotting, Western/methods
MH  - Cell Line
MH  - Cloning, Molecular/methods
MH  - Disks Large Homolog 4 Protein
MH  - Drug Interactions
MH  - Flow Cytometry/methods
MH  - Fluorescent Antibody Technique/methods
MH  - Gene Expression Regulation/*drug effects/physiology
MH  - Genetic Vectors/pharmacology/physiology
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Ketamine/*pharmacology
MH  - Luminescent Proteins/metabolism
MH  - Membrane Proteins
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neurotoxins/*pharmacology
MH  - Peptide Fragments/physiology
MH  - Protein Structure, Tertiary/physiology
MH  - Rats
MH  - *Receptors, N-Methyl-D-Aspartate/chemistry/classification/physiology
MH  - Recombinant Fusion Proteins/physiology
MH  - Transfection/methods
EDAT- 2005/04/02 09:00
MHDA- 2005/07/06 09:00
CRDT- 2005/04/02 09:00
PHST- 2004/11/04 00:00 [accepted]
PHST- 2005/04/02 09:00 [pubmed]
PHST- 2005/07/06 09:00 [medline]
PHST- 2005/04/02 09:00 [entrez]
AID - S0306-4522(04)01085-1 [pii]
AID - 10.1016/j.neuroscience.2004.11.049 [doi]
PST - ppublish
SO  - Neuroscience. 2005;132(2):281-98. doi: 10.1016/j.neuroscience.2004.11.049.