The Arg473Cys-neuroligin-1 mutation modulates NMDA mediated synaptic transmission and receptor distribution in hippocampal neurons.
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.
Khosravani
Houman
H
Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, HMRB 182b, 3330 Hospital Dr. NW Calgary, Alta., Canada T2N 4N1.
Altier
Christophe
C
Zamponi
Gerald W
GW
Colicos
Michael A
MA
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal; D002478:Cells, Cultured; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology*; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D020125:Mutation, Missense / Q000502:physiology*; D016202:N-Methylaspartate / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics*; D014018:Tissue Distribution; D014162:Transfection
D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C093438:neuroligin 1; D016202:N-Methylaspartate