Sequences in the amino termini of GABA ρ and GABA(A) subunits specify their selective interaction in vitro

Abigail S. Hackam, Tian Li Wang, William B. Guggino, Garry R. Cutting

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Molecular cloning has revealed that there are six classes of subunits capable of forming GABA-gated chloride channel receptors. GABA(A) receptors are composed of α, β, γ, δ, and ε/χ subunits, whereas GABA(c) receptors appear to contain ρ subunits. However, retinal cells exhibiting GABA(c) responses express α, β, and ρ subunits, raising the possibility that GABA(c) receptors may be a mixture of subunit classes. Using in vitro translated protein, we determined that human GABA(A) receptor subunits α1, α5, and β1 did not coimmunoprecipitate with full-length ρ1, ρ2, or the N- terminal domain of ρ1 that contains signals for ρ-subunit interaction. To explore the molecular mechanism underlying these apparently exclusive combinations, chimeric subunits were created and tested for interaction with the wild-type subunits. Transfer of the N terminus of β1 to ρ1 created a β1ρ1 chimera that coimmunoprecipitated with the α1 subunit but not with the ρ2 subunit. Furthermore, exchanging the N terminus of the ρ1 subunit with the corresponding region of β1 produced a ρ1β1 chimera that interfered with ρ1 receptor expression in Xenopus oocytes, whereas the full- length β1 subunit had no effect. Together, these results indicate that sequences in the N termini direct assembly of ρ subunits and GABA(A) subunits into GABA(C) and GABA(A) receptors, respectively.

Original languageEnglish (US)
Pages (from-to)40-46
Number of pages7
JournalJournal of neurochemistry
Volume70
Issue number1
DOIs
StatePublished - Jan 1998

Keywords

  • Ligand-gated ion channel
  • Molecular composition
  • Retinal neurotransmission

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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