Spectrin-beta 2 facilitates the selective accumulation of GABA A receptors at somatodendritic synapses.
Communications biology(2023)
摘要
Fast synaptic inhibition is dependent on targeting specific GABAR subtypes to dendritic and axon initial segment (AIS) synapses. Synaptic GABARs are typically assembled from α1-3, β and γ subunits. Here, we isolate distinct GABARs from the brain and interrogate their composition using quantitative proteomics. We show that α2-containing receptors co-assemble with α1 subunits, whereas α1 receptors can form GABARs with α1 as the sole α subunit. We demonstrate that α1 and α2 subunit-containing receptors co-purify with distinct spectrin isoforms; cytoskeletal proteins that link transmembrane proteins to the cytoskeleton. β2-spectrin was preferentially associated with α1-containing GABARs at dendritic synapses, while β4-spectrin was associated with α2-containing GABARs at AIS synapses. Ablating β2-spectrin expression reduced dendritic and AIS synapses containing α1 but increased the number of synapses containing α2, which altered phasic inhibition. Thus, we demonstrate a role for spectrins in the synapse-specific targeting of GABARs, determining the efficacy of fast neuronal inhibition.
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