Identification of 70 amino acids important for GABAC receptor ρ1 sub-unit assembly

gamma-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the mammalian central nervous system and gates at least three subclasses of receptors, termed GABA(A), GABA(B) and GABA(C). Accumulating evidence indicates that GABA(C) receptors are composed exclusively of rho subunits. The N-terminal half of the rho subunits has been shown to mediate formation of homo- and heterooligomeric GABA(C) receptors. In this study, we searched for specific sequences within the N-terminus of the rho 1 subunit involved in the assembly process. Assembly sequences were localized to a 128-amino acid region by deletion of progressively larger regions of a chimeric rho 1 beta 1 subunit previously shown to disrupt rho 1 and rho 2 assembly. To confirm this observation, a series of GABA(A) receptor beta subunit chimeras containing different regions of the rho 1 N-terminus were tested for interference with rho 1 and rho 2 subunit assembly into functional GABA receptors. Transfer of 70 residues within the 128 amino acid region to the beta 1 subunit created a chimera that disrupted rho 1, but not rho 2, assembly into functional receptors. These observations refine the location of signals involved in rho 1 subunit assembly, and suggest that different signals exist for the formation of rho 1 homooligomeric and rho 1/rho 2 heterooligomeric GABA(C) receptors. (C) 1999 Elsevier Science B.V. All rights reserved.