Subunit Arrangement of γ-Aminobutyric Acid Type A Receptors

• Published in: The Journal of biological chemistry Vol. 276; no. 39; p. 36275
• Main Authors: Sabine W. Baumann, Roland Baur, Erwin Sigel
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 28.09.2001
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M105240200

The GABA A receptors are ligand-gated chloride channels. The subunit stoichiometry of the receptors is controversial; four, five, or six subunits per receptor molecule have been proposed for αβ receptors, whereas αβγ receptors are assumed to be pentamers. In this study, α-β and β-α tandem cDNAs from the α1 and β2 subunits of the GABA A receptor were constructed. We determined the minimal length of the linker that is required between the two subunits for functional channel expression for each of the tandem constructs. 10- and 23-amino acid residues are required for α-β and β-α, respectively. The tandem constructs either alone or in combination with each other failed to express functional channels in Xenopus oocytes. Therefore, we can exclude tetrameric or hexameric αβ GABA A receptors. We can also exclude proteolysis of the tandem constructs. In addition, the tandem constructs were combined with single α, β, or γ subunits to allow formation of pentameric arrangements. In contrast to the combination with α subunits, the combination with either β or γ subunits led to expression of functional channels. Therefore, a pentameric arrangement containing two α1 and three β2 subunits is proposed for the receptor composed of α and β subunits. Our findings also favor an arrangement βαγβα for the receptor composed of α, β, and γ subunits.