Gephyrin:a scaffold that builds a phase at the inhibitory postsynapses

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The scaffolding protein gephyrin is a core component of many inhibitory synapses.Bai and colleagues now show that phase separation of gephyrin with the subunits of both glycine and GABA receptors underlies the formation of postsynaptic sheets at the inhibitory synapses.To assure precise processing of information,contacts between neurons require the alignment of the release sites,presynaptic terminals,with the ionotropic transmitter receptors at the postsynaptic plasma membrane.Downstream of these receptors,scaffold molecules,kinases and cytoskeleton components all orchestrate the signaling cascade induced by the neurotransmitter binding and ion influx.Each neuron in the mammalian central nervous system relies on both the excitatory and inhibitory inputs.A long-standing view is that the postsynaptic density (PSD)represents a hallmark of the excitatory synapses.Recent cryo-electron tomography work suggested that even the inhibitory synapses contain thin-sheet densities of-5nm,so-called iPSD,underneath the clusters of glycine receptor (GlyR) and type-A y-aminobutyric acid receptor (GABAAR).1
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