Assembly rules for GABAA receptor complexes in the brain

James S. Martenson, Tokiwa Yamasaki, Nashid H. Chaudhury, David Albrecht, Susumu Tomita

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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, a 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.

Original languageEnglish
Article numbere27443
JournaleLife
Volume6
DOIs
Publication statusPublished - 2017 Aug 17
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Martenson, J. S., Yamasaki, T., Chaudhury, N. H., Albrecht, D., & Tomita, S. (2017). Assembly rules for GABAA receptor complexes in the brain. eLife, 6, [e27443]. https://doi.org/10.7554/eLife.27443