Mechanisms underlying synapse-specific clustering of GABAA receptors


Prof A. M. Thomson, as above.


A principle that arises from a body of previous work is that each presynaptic terminal recognises its postsynaptic partner and that each postsynaptic site recognises the origin of the synaptic bouton innervating it. In response, the presynaptic terminal sequesters the proteins whose interactions result in the dynamic transmitter release pattern and chemical modulation appropriate for that connection. In parallel, the postsynaptic site sequesters, inserts or captures the receptors and postsynaptic density proteins appropriate for that type of synapse. The focus of this review is the selective clustering of GABAA receptors (GABAAR) at synapses made by each class of inhibitory interneurone. This provides a system in which the mechanisms underlying transynaptic recognition can be explored. There are many synaptic proteins, often with several isoforms created by post-translational modifications. Complex cascades of interactions between these proteins, on either side of the synaptic cleft, are essential for normal function, normal transmitter release and postsynaptic responsiveness. Interactions between presynaptic and postsynaptic proteins that have binding domains in the synaptic cleft are proposed here to result in a local cleft structure that captures and stabilises only the appropriate subtype of GABAARs, allowing others to drift away from that synapse, either to be captured by another synapse, or internalised.