Molecular Determinants of NMDA Receptor Internalization

Nat Neurosci. 2001 Aug;4(8):794-802. doi: 10.1038/90498.

Abstract

Although synaptic AMPA receptors have been shown to rapidly internalize, synaptic NMDA receptors are reported to be static. It is not certain whether NMDA receptor stability at synaptic sites is an inherent property of the receptor, or is due to stabilization by scaffolding proteins. In this study, we demonstrate that NMDA receptors are internalized in both heterologous cells and neurons, and we define an internalization motif, YEKL, on the distal C-terminus of NR2B. In addition, we show that the synaptic protein PSD-95 inhibits NR2B-mediated internalization, and that deletion of the PDZ-binding domain of NR2B increases internalization in neurons. This suggests an involvement for PSD-95 in NMDA receptor regulation and an explanation for NMDA receptor stability at synaptic sites.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs / physiology
  • Animals
  • Binding Sites / physiology
  • Central Nervous System / metabolism*
  • Central Nervous System / ultrastructure
  • Clathrin / metabolism
  • Disks Large Homolog 4 Protein
  • Endocytosis / physiology*
  • Fetus
  • HeLa Cells / cytology
  • HeLa Cells / metabolism
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Protein Structure, Tertiary / physiology
  • Protein Transport / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / chemistry*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / ultrastructure
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Synaptic Membranes / metabolism*
  • Synaptic Membranes / ultrastructure

Substances

  • Clathrin
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NR1 NMDA receptor
  • NR2B NMDA receptor
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Recombinant Fusion Proteins
  • postsynaptic density proteins