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GABAA receptor (GABAAR) pentamers are assembled from a pool of 19 subunits, and variety in subunit combinations diversifies GABAAR functions to tune brain activity. Pentamers with distinct subunit compositions localize differentially at synaptic and non-synaptic sites to mediate phasic and tonic inhibition, respectively. Despite multitudes of theoretical permutations, limited subunit combinations have been identified in the brain. Currently, no molecular model exists for combinatorial GABAAR assembly in vivo. Here, we reveal assembly rules of native GABAAR complexes that explain GABAAR subunit subcellular distributions using mice and Xenopus laevis oocytes. First, α subunits possess intrinsic signals to segregate into distinct pentamers. Second, γ2 is essential for GABAAR assembly with Neuroligin-2 (NL2) and GARLHs, which localize GABAARs at synapses. Third, δ suppresses α6 synaptic localization by preventing assembly with GARLHs/NL2. These findings establish the first molecular model for combinatorial GABAAR assembly in vivo and reveal an assembly pathway regulating GABAAR synaptic localization.
Pubmed ID: 28816653 RIS Download
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View all literature mentionsCenter that imports, archives, maintains, and distributes mutant mouse alleles as live mice, frozen germplasm, stem cells, and molecular vectors for use in biomedical research. The MMRRC Davis receives transgenics, knockouts, and other kinds of mutant mouse lines at no cost to the donor, and after re-derivation and cryopreservation, distributes breeding stock, germplasm, cells, or tissues of genetically-defined and pathogen-free mice for a small fee to requesting investigators.
View all literature mentionsThis monoclonal targets Gephyrin
View all literature mentionsThis monoclonal targets Gephyrin
View all literature mentionsThis polyclonal targets VGAT (cytoplasmic domain)
View all literature mentionsThis polyclonal targets Neuroligin 2
View all literature mentionsThis monoclonal targets HA
View all literature mentionsThis unknown targets GABAA Receptor delta-subunit
View all literature mentionsThis polyclonal targets GABA A Receptor gamma2 cytoplasmic loop
View all literature mentionsThis unknown targets GABA (A) alpha6 Receptor (extracellular)
View all literature mentionsThis polyclonal targets GABA A Receptor alpha6
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View all literature mentionsThis monoclonal targets GABA(A)R, Alpha1
View all literature mentionsThis monoclonal targets GABA A Receptor beta2/3 clone 62-3G1
View all literature mentionsMus musculus with name B6.129P2-Gabra6tm2(cre)Wwis/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6.D2-Tg(Gabra6-cre)B1Lfr/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6.Cg-Tg(CAG-cre/Esr1*)5Amc/J from IMSR.
View all literature mentionsMus musculus with name B6;129-Gabrdtm1.1Jmag/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name B6.129P2-Gabra6tm2(cre)Wwis/Mmucd from MMRRC.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis unknown targets
View all literature mentionsMus musculus with name B6.D2-Tg(Gabra6-cre)B1Lfr/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6.Cg-Tg(CAG-cre/Esr1*)5Amc/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2-Gabra6tm2(cre)Wwis/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6.D2-Tg(Gabra6-cre)B1Lfr/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6.Cg-Tg(CAG-cre/Esr1*)5Amc/J from IMSR.
View all literature mentionsMus musculus with name B6.D2-Tg(Gabra6-cre)B1Lfr/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6.Cg-Tg(CAG-cre/Esr1*)5Amc/J from IMSR.
View all literature mentionsMus musculus with name B6;129-Gabrdtm1.1Jmag/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name B6;129-Gabrdtm1.1Jmag/J from IMSR.
View all literature mentionsMus musculus with name B6;129-Gabrdtm1.1Jmag/J from IMSR.
View all literature mentionsThis monoclonal targets Gephyrin
View all literature mentionsThis monoclonal targets Gephyrin
View all literature mentionsThis unknown targets GABA (A) alpha6 Receptor (extracellular)
View all literature mentionsThis polyclonal targets GABA A Receptor gamma2 cytoplasmic loop
View all literature mentionsThis polyclonal targets VGAT (cytoplasmic domain)
View all literature mentionsThis monoclonal targets GABA A Receptor beta2/3 clone 62-3G1
View all literature mentionsThis monoclonal targets HA
View all literature mentionsThis polyclonal targets Neuroligin 2
View all literature mentionsThis monoclonal targets GABA A Receptor beta2/3 clone 62-3G1
View all literature mentionsThis unknown targets GABAA Receptor delta-subunit
View all literature mentionsThis monoclonal targets Gephyrin
View all literature mentionsThis monoclonal targets Gephyrin
View all literature mentionsThis polyclonal targets VGAT (cytoplasmic domain)
View all literature mentionsThis monoclonal targets GABA(A)R, Alpha1
View all literature mentionsThis polyclonal targets GABA A Receptor alpha 1
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets GABA(A)R, Alpha1
View all literature mentionsThis monoclonal targets GABA A Receptor beta2/3 clone 62-3G1
View all literature mentionsThis polyclonal targets GABA A Receptor alpha6
View all literature mentionsThis polyclonal targets GABA A Receptor alpha6
View all literature mentionsThis polyclonal targets Neuroligin 2
View all literature mentionsThis polyclonal targets GABA A Receptor alpha 1
View all literature mentionsThis monoclonal targets HA
View all literature mentionsThis unknown targets GABAA Receptor delta-subunit
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets GABA A Receptor gamma2 cytoplasmic loop
View all literature mentionsThis monoclonal targets GABA(A)R, Alpha1
View all literature mentionsThis unknown targets GABA (A) alpha6 Receptor (extracellular)
View all literature mentionsMus musculus with name B6.129P2-Gabra6tm2(cre)Wwis/Mmucd from MMRRC.
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