Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons

Nature. 1993 Dec 23-30;366(6457):745-8. doi: 10.1038/366745a0.


Each neuron in the mammalian brain carries many postsynaptic membrane specializations containing high densities of receptors that mediate signal transduction upon neurotransmitter release from the apposed nerve terminal. Little is known about the mechanisms by which receptors are transported to and anchored at postsynaptic sites, but extracellular as well as intracellular components may be involved. Ultrastructural studies have shown that the peripheral membrane protein gephyrin, which co-purifies with the postsynaptic inhibitory glycine receptor (GlyR) upon affinity chromatography, is situated on the cytoplasmic face of glycinergic postsynaptic membranes. Moreover, gephyrin binds with high affinity to polymerized tubulin and has been postulated to link the GlyR to the subsynaptic cytoskeleton. Here we report that treatment of rat spinal neurons in culture with gephyrin antisense oligonucleotides prevents the formation of GlyR clusters in the dendritic plasma membrane. Thus, gephyrin is essential for localizing the GlyR to presumptive postsynaptic plasma membrane specializations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Dendrites / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Microscopy, Fluorescence
  • Neurons / metabolism*
  • Oligonucleotides, Antisense
  • Rats
  • Rats, Wistar
  • Receptor Aggregation*
  • Receptors, Glycine / metabolism*
  • Spinal Cord / cytology
  • Spinal Cord / metabolism*
  • Synaptic Membranes / metabolism


  • Carrier Proteins
  • Membrane Proteins
  • Oligonucleotides, Antisense
  • Receptors, Glycine
  • gephyrin