The Arg473Cys-neuroligin-1 mutation modulates NMDA mediated synaptic transmission and receptor distribution in hippocampal neurons

FEBS Lett. 2005 Dec 5;579(29):6587-94. doi: 10.1016/j.febslet.2005.10.051. Epub 2005 Nov 9.


Synapses mediate communication between neurons, thus playing a fundamental role in information processing in the CNS. Neuroligins form a family of heterophilic synaptic cell adhesion molecules, and neuroligin 1 (NL1) has been shown to be involved in the formation of excitatory synapses and have been suggested to associate indirectly with NMDA receptors by common binding to PSD95. A mutation in neuroligin 3 (Arg451Cys-NL3, human sequence numbering) identified in autistic patients is associated with altered spine density and has reduced binding capacity for its presynaptic partner beta-neurexin. Here, we investigated the role of NL1 and the homologous NL1 mutation Arg473Cys-NL1 (R473C-NL1) in excitatory synaptic transmission and NMDA receptor distribution. We demonstrate that R473C-NL1, when expressed in cultured hippocampal neurons, can induce a dramatic increase in NMDA current amplitude and that this change is accompanied by NMDA receptor clustering in the postsynaptic cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal
  • Cells, Cultured
  • Electrophysiology
  • Hippocampus / cytology*
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology
  • Mice
  • Mutation, Missense / physiology*
  • N-Methylaspartate / physiology*
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / physiology
  • Neurons / chemistry
  • Neurons / physiology*
  • Rats
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synaptic Transmission / genetics*
  • Tissue Distribution
  • Transfection


  • Cell Adhesion Molecules, Neuronal
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • neuroligin 1
  • N-Methylaspartate