TY - JOUR
T1 - GARLH Family Proteins Stabilize GABAA Receptors at Synapses
AU - Yamasaki, Tokiwa
AU - Hoyos-Ramirez, Erika
AU - Martenson, James S.
AU - Morimoto-Tomita, Megumi
AU - Tomita, Susumu
N1 - Funding Information:
The authors thank Dr. Satinder Singh for providing her valuable input and the members of the Tomita lab for discussions. We thank Dr. Louis Reichardt for sharing transgenic Cre mice under the GABAAR α6 promoter through the MMRRC, Dr. Bernhard Luscher for conditional γ2 mice, Dr. Feng Zhang for Cre-dependent Cas9 knockin mice through the Jackson Laboratory, Addgene for the plasmids listed in the STAR Methods and the University of California, Davis/NeuroMab Facility (NIH U24NS050606), for the antibodies. This work was supported by NIH/NIMH MH104984, Yale University (S.T.), and research fellowships from the Japan Society for the Promotion of Science and the Uehara Memorial Foundation (T.Y.), NIH F30 MH099742, and NIH T32GM007205 (J.S.M.).
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/3/8
Y1 - 2017/3/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuron.2017.02.023
DO - 10.1016/j.neuron.2017.02.023
M3 - Article
C2 - 28279354
AN - SCOPUS:85014797725
SN - 0896-6273
VL - 93
SP - 1138-1152.e6
JO - Neuron
JF - Neuron
IS - 5
ER -