Pre- and post-synaptic mechanisms regulating the clustering of type A γ-aminobutyric acid receptors (GABA_A receptors)

Postsynaptic clustering of GABA_A (type A γ-aminobutyric acid) receptors is essential to ensure proper function of GABAergic synapses. This process is initiated during synapse formation and is maintained throughout life. The tubulin-associated protein gephyrin is required for clustering of GABA_A receptors, but its specific role in this process is not understood. A second protein associated selectively with GABA_A receptors at postsynaptic sites is dystrophin. It is present in a subset of GABAergic synapses along with several partners, forming the dystrophin-associated protein complex. In this review, we discuss recent advances in the role of neuronal activity and trans-synaptic signaling for the clustering of gephyrin and dystrophin during synaptogenesis and on the role of these proteins for plasticity and maintenance of mature synapses.