GABAergic Terminals Are Required for Postsynaptic Clustering of Dystrophin But Not of GABAA Receptors and Gephyrin

• Published in: The Journal of neuroscience Vol. 22; no. 12; pp. 4805 - 4813
• Main Authors: Brunig, Ina, Suter, Anthi, Knuesel, Irene, Luscher, Bernhard, Fritschy, Jean-Marc
• Format: Journal Article
• Language: English
• Published: Soc Neuroscience 15.06.2002; Society for Neuroscience
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.22-12-04805.2002

In rat hippocampal cultures, we show by multilabeling immunocytochemistry that pyramidal cells, which receive little or no GABAergic input, mistarget α 2 -GABA A receptors and gephyrin to glutamatergic terminals. This mismatch does not occur in neurons innervated by numerous GABAergic terminals. A similar phenomenon has been reported for isolated autaptic hippocampal neurons ( Rao et al., 2000 ). GABAergic synapses typically form multiple release sites apposed to GABA A receptor and gephyrin clusters. Remarkably, dystrophin, a protein highly abundant in skeletal muscle membranes, is extensively colocalized with α 2 -GABA A receptors exclusively opposite GABAergic terminals. In addition, selective apposition of syntrophin and β-dystroglycan to GABAergic presynaptic terminals suggests that the entire dystrophin-associated protein complex (DPC) clusters at GABAergic synapses. In contrast to gephyrin and GABA A receptors, DPC proteins are not mistargeted to glutamatergic synapses, indicating independent clustering mechanisms. This was confirmed in hippocampal neurons cultured from GABA A receptor γ 2 subunit-deficient mice. Clustering of GABA A receptor and gephyrin in these neurons was strongly impaired, whereas clustering of dystrophin and associated proteins was unaffected by the absence of the γ 2 subunit. Our results indicate that accumulation of dystrophin and DPC proteins at GABAergic synapses occurs independently of postsynaptic GABA A receptors and gephyrin. We suggest that selective signaling from GABAergic terminals contributes to postsynaptic clustering of dystrophin.