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GARLH Family Proteins Stabilize GABAA Receptors at Synapses.

Neuron | Mar 8, 2017

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.

Pubmed ID: 28279354 RIS Download

Mesh terms: Animals | Cells, Cultured | Hippocampus | Humans | Mice, Inbred C57BL | Mice, Transgenic | Neurotransmitter Agents | Protein Subunits | Receptors, GABA-A | Synapses | Synaptic Transmission

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Associated grants

  • Agency: NIMH NIH HHS, Id: F30 MH099742
  • Agency: NCATS NIH HHS, Id: UL1 TR001863
  • Agency: NINDS NIH HHS, Id: U24 NS050606
  • Agency: NIGMS NIH HHS, Id: T32 GM007205
  • Agency: NIMH NIH HHS, Id: U01 MH104984

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