Assembly rules for GABAA receptor complexes in the brain

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

研究成果: Article査読

32 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号e27443
ジャーナルeLife
6
DOI
出版ステータスPublished - 2017 8月 17
外部発表はい

ASJC Scopus subject areas

  • 神経科学(全般)
  • 免疫学および微生物学(全般)
  • 生化学、遺伝学、分子生物学(全般)

フィンガープリント

「Assembly rules for GABAA receptor complexes in the brain」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル