| First Author | Smalley JL | Year | 2023 |
| Journal | Commun Biol | Volume | 6 |
| Issue | 1 | Pages | 11 |
| PubMed ID | 36604600 | Mgi Jnum | J:336217 |
| Mgi Id | MGI:7423956 | Doi | 10.1038/s42003-022-04381-x |
| Citation | Smalley JL, et al. (2023) Spectrin-beta 2 facilitates the selective accumulation of GABA(A) receptors at somatodendritic synapses. Commun Biol 6(1):11 |
| abstractText | Fast synaptic inhibition is dependent on targeting specific GABA(A)R subtypes to dendritic and axon initial segment (AIS) synapses. Synaptic GABA(A)Rs are typically assembled from alpha1-3, beta and gamma subunits. Here, we isolate distinct GABA(A)Rs from the brain and interrogate their composition using quantitative proteomics. We show that alpha2-containing receptors co-assemble with alpha1 subunits, whereas alpha1 receptors can form GABA(A)Rs with alpha1 as the sole alpha subunit. We demonstrate that alpha1 and alpha2 subunit-containing receptors co-purify with distinct spectrin isoforms; cytoskeletal proteins that link transmembrane proteins to the cytoskeleton. beta2-spectrin was preferentially associated with alpha1-containing GABA(A)Rs at dendritic synapses, while beta4-spectrin was associated with alpha2-containing GABA(A)Rs at AIS synapses. Ablating beta2-spectrin expression reduced dendritic and AIS synapses containing alpha1 but increased the number of synapses containing alpha2, which altered phasic inhibition. Thus, we demonstrate a role for spectrins in the synapse-specific targeting of GABA(A)Rs, determining the efficacy of fast neuronal inhibition. |
