Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses through gephyrin and collybistin

Neuron. 2009 Sep 10;63(5):628-42. doi: 10.1016/j.neuron.2009.08.023.

Abstract

In the mammalian CNS, each neuron typically receives thousands of synaptic inputs from diverse classes of neurons. Synaptic transmission to the postsynaptic neuron relies on localized and transmitter-specific differentiation of the plasma membrane with postsynaptic receptor, scaffolding, and adhesion proteins accumulating in precise apposition to presynaptic sites of transmitter release. We identified protein interactions of the synaptic adhesion molecule neuroligin 2 that drive postsynaptic differentiation at inhibitory synapses. Neuroligin 2 binds the scaffolding protein gephyrin through a conserved cytoplasmic motif and functions as a specific activator of collybistin, thus guiding membrane tethering of the inhibitory postsynaptic scaffold. Complexes of neuroligin 2, gephyrin and collybistin are sufficient for cell-autonomous clustering of inhibitory neurotransmitter receptors. Deletion of neuroligin 2 in mice perturbs GABAergic and glycinergic synaptic transmission and leads to a loss of postsynaptic specializations specifically at perisomatic inhibitory synapses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / physiology
  • COS Cells
  • Carrier Proteins / metabolism*
  • Cell Adhesion Molecules, Neuronal
  • Cell Line
  • Cells, Cultured
  • Chlorocebus aethiops
  • Dendrites / physiology
  • Glutamic Acid / metabolism
  • Glycine / metabolism
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • In Vitro Techniques
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Models, Neurological
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / physiology*
  • Rats
  • Receptors, GABA-A / metabolism
  • Rho Guanine Nucleotide Exchange Factors
  • Synapses / physiology*
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Arhgef9 protein, mouse
  • Arhgef9 protein, rat
  • Carrier Proteins
  • Cell Adhesion Molecules, Neuronal
  • Guanine Nucleotide Exchange Factors
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, GABA-A
  • Rho Guanine Nucleotide Exchange Factors
  • gephyrin
  • neuroligin 2
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Glycine