The promiscuous role of the epsilon subunit in GABA(A) receptor biogenesis

The formation of alpha 1 beta 2 gamma 2 epsilon receptors suggests that the e subunit does not displace the single gamma 2 subunit in alpha 1 beta 2 gamma 2 receptors. Thus, e must replace cc and/or beta subunit(s) if the pentameric receptor structure is to be preserved. To assess the potential for which subunit is replaced in alpha beta epsilon and alpha beta gamma epsilon receptors we analyzed the assembly and functional expression of the e subunit with respect to alpha 1, beta 2 and gamma 2 subunits. Using concatenated subunits, we have determined that e is capable of substituting for either (but not both) of the alpha subunits, one of the 0 subunits, and possibly the gamma 2 subunit. However, the most likely sites at which the e subunit may contribute to receptor function appears to be at position I (replaces alpha 1) in alpha beta gamma epsilon (epsilon-beta 2-alpha 1-beta 2-gamma 2) receptors, or at position 4 (replaces beta 2) in alpha beta epsilon (alpha 1-beta 2-alpha 1-epsilon-beta 2) receptors. In both cases, it appears that only a single GABA binding site is present. (c) 2007 Elsevier Inc. All rights reserved.