Dataset Information

Spectrin-beta 2 facilitates the selective accumulation of GABAA receptors at somatodendritic synapses

ABSTRACT: Fast synaptic inhibition is dependent on targeting specific GABAAR subtypes to dendritic and axon initial segment (AIS) synapses. Synaptic GABAARs are typically assembled from 1-3, and subunits. Here, we isolate distinct GABAARs 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 GABAARs with α1 as the sole 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 GABAARs at dendritic synapses, while β4-spectrin was associated with 2-containing GABAARs 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 GABAARs, determining the efficacy of fast neuronal inhibition.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Cerebral Cortex Pyramidal Neuron

SUBMITTER: Joshua Smalley

LAB HEAD: Stephen J Moss

PROVIDER: PXD038703 | Pride | 2023-03-10

REPOSITORIES: Pride

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Publications

Spectrin-beta 2 facilitates the selective accumulation of GABAA receptors at somatodendritic synapses.

Smalley Joshua L JL Cho Noell N Ng Shu Fun Josephine SFJ Choi Catherine C Lemons Abigail H S AHS Chaudry Saad S Bope Christopher E CE Dengler Jake S JS Zhang Chuansheng C Rasband Matthew N MN Davies Paul A PA Moss Stephen J SJ

Communications biology 20230105 1

Fast synaptic inhibition is dependent on targeting specific GABAAR subtypes to dendritic and axon initial segment (AIS) synapses. Synaptic GABAARs are typically assembled from α1-3, β and γ subunits. Here, we isolate distinct GABAARs 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 GABAARs with α1 as the sole α subunit. We dem ...[more]

PMID: 36604600

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Dataset Information

Spectrin-beta 2 facilitates the selective accumulation of GABAA receptors at somatodendritic synapses

Publications

Spectrin-beta 2 facilitates the selective accumulation of GABA<sub>A</sub> receptors at somatodendritic synapses.

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