GARLH Family Proteins Stabilize GABAA Receptors at Synapses

Tokiwa Yamasaki, Erika Hoyos-Ramirez, James S. Martenson, Megumi Morimoto-Tomita, Susumu Tomita

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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.

Original languageEnglish
Pages (from-to)1138-1152.e6
JournalNeuron
Volume93
Issue number5
DOIs
Publication statusPublished - 2017 Mar 8

ASJC Scopus subject areas

  • Neuroscience(all)

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    Yamasaki, T., Hoyos-Ramirez, E., Martenson, J. S., Morimoto-Tomita, M., & Tomita, S. (2017). GARLH Family Proteins Stabilize GABAA Receptors at Synapses. Neuron, 93(5), 1138-1152.e6. https://doi.org/10.1016/j.neuron.2017.02.023