Laminar organization of the NMDA receptor complex within the postsynaptic density.
The NR2 subunit is an essential component of the NMDA receptor. Recent biochemical research has identified a number of molecules that can bind directly or indirectly to its cytoplasmic tail. These postsynaptic density (PSD) proteins play a role in intracellular signal transduction, and are implicated in synaptic plasticity and memory mechanisms. We performed systematic electron microscopic immunogold analysis in rat neocortex to determine the spatial organization of NR2, in relation to six other proteins thought to be involved in the NMDA receptor complex. Peak concentrations of each protein were within the PSD but in different "layers" of the density. In the axodendritic axis, gold particles coding for PSD-95 lay an average of 12 nm cytoplasmic to the extracellular face of the plasma membrane, very close to the C terminal of NR2. Nitric oxide synthase lay 18 nm inside the membrane; the scaffolding proteins guanylate kinase-associated protein and Shank lay 24-26 nm inside the membrane; and CRIPT and dynein light chain, proteins that may link the complex to cytoskeletal elements, lay on the cytoplasmic side of the PSD, 29-32 nm inside the plasma membrane and extending into the spine cytoplasm. The supramolecular organization of these molecules may modulate intracellular transduction of NMDA-mediated signals.
Valtschanoff
J G
JG
Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill, North Carolina 27599, USA. jval@med.unc.edu
Weinberg
R J
RJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis; D002462:Cell Membrane / Q000648:ultrastructure; D003593:Cytoplasm / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D029721:Drosophila Proteins; D004398:Dyneins; D006046:Gold; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008854:Microscopy, Electron; D019579:Neocortex / Q000737:chemistry / Q000648:ultrastructure*; D009419:Nerve Tissue Proteins / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000032:analysis; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000648:ultrastructure*; D000074407:SAP90-PSD95 Associated Proteins; D013569:Synapses / Q000737:chemistry / Q000648:ultrastructure*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C484742:Cript protein, rat; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000614192:Mars protein, Drosophila; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D000074407:SAP90-PSD95 Associated Proteins; C033652:postsynaptic density proteins; D006046:Gold; D019001:Nitric Oxide Synthase; D004398:Dyneins