Nature 366, 745 - 748 (30 December 1993); doi:10.1038/366745a0

Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons

J. Kirsch, I. Wolters, A. Triller^* & H. Betz^†

Department of Neurochemistry, Max-Planck-lnstitute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt/Main, Germany
^*Neurobiologie Cellulaire, Inserm U261, Departement des Biotechnologies, Institut Pasteur, 28 rue du Dr Roux, 750 Paris Cedex 15, France
^†To whom correspondence should be addressed.

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 terminal¹. Little is known about the mechanisms by which receptors are transported to and anchored at postsynaptic sites, but extracellular² as well as intracellular³ components may be involved. Ultrastructural studies have shown that the peripheral membrane protein gephyrin⁴, which co-purifies with the postsynaptic inhibitory glycine receptor (GlyR) upon affinity chromatography^5,6, is situated on the cytoplasmic face of glycinergic postsynaptic membranes^7–9. Moreover, gephyrin binds with high affinity to polymerized tubulin and has been postulated to link the GlyR to the subsynaptic cytoskeleton¹⁰. 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.

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