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Neuron. 2017 Mar 8;93(5):1138-1152.e6. doi: 10.1016/j.neuron.2017.02.023.

GARLH Family Proteins Stabilize GABAA Receptors at Synapses.

Author information

1
Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA.
2
Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: susumu.tomita@yale.edu.

Abstract

Ionotropic neurotransmitter receptors mediate fast synaptic transmission by functioning as ligand-gated ion channels. Fast inhibitory transmission in the brain is mediated mostly by ionotropic GABAA receptors (GABAARs), but their essential components for synaptic localization remain unknown. Here, we identify putative auxiliary subunits of GABAARs, which we term GARLHs, consisting of LH4 and LH3 proteins. LH4 forms a stable tripartite complex with GABAARs and neuroligin-2 in the brain. Moreover, LH4 is required for the synaptic localization of GABAARs and inhibitory synaptic transmission in the hippocampus. Our findings propose GARLHs as the first identified auxiliary subunits for anion channels. These findings provide new insights into the regulation of inhibitory transmission and the molecular constituents of native anion channels in vivo.

PMID:
28279354
PMCID:
PMC5347473
[Available on 2018-03-08]
DOI:
10.1016/j.neuron.2017.02.023
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