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

Ina Brünig, Anthi Suter, Irene Knuesel, Bernhard Luscher, Jean Marc Fritschy

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Abstract

In rat hippocampal cultures, we show by multilabeling immunocytochemistry that pyramidal cells, which receive little or no GABAergic input, mistarget α2-GABAA 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 GABAA receptor and gephyrin clusters. Remarkably, dystrophin, a protein highly abundant in skeletal muscle membranes, is extensively colocalized with α2-GABAA 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 GABAA receptors, DPC proteins are not mistargeted to glutamatergic synapses, indicating independent clustering mechanisms. This was confirmed in hippocampal neurons cultured from GABAA receptor γ2 subunit-deficient mice. Clustering of GABAA receptor and gephyrin in these neurons was strongly impaired, whereas clustering of dystrophin and associated proteins was unaffected by the absence of the γ2 subunit. Our results indicate that accumulation of dystrophin and DPC proteins at GABAergic synapses occurs independently of postsynaptic GABAA receptors and gephyrin. We suggest that selective signaling from GABAergic terminals contributes to postsynaptic clustering of dystrophin.

Original languageEnglish (US)
Pages (from-to)4805-4813
Number of pages9
JournalJournal of Neuroscience
Volume22
Issue number12
DOIs
StatePublished - Jun 15 2002

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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