The promiscuous role of the epsilon subunit in GABAA receptor biogenesis.
The formation of alpha1beta2gamma2epsilon receptors suggests that the epsilon subunit does not displace the single gamma2 subunit in alpha1beta2gamma2 receptors. Thus, epsilon must replace alpha and/or beta subunit(s) if the pentameric receptor structure is to be preserved. To assess the potential for which subunit is replaced in alphabetaepsilon and alphabetagammaepsilon receptors we analyzed the assembly and functional expression of the epsilon subunit with respect to alpha1, beta2 and gamma2 subunits. Using concatenated subunits, we have determined that epsilon is capable of substituting for either (but not both) of the alpha subunits, one of the beta subunits, and possibly the gamma2 subunit. However, the most likely sites at which the epsilon subunit may contribute to receptor function appears to be at position 1 (replaces alpha1) in alphabetagammaepsilon (epsilon-beta2-alpha1-beta2-gamma2) receptors, or at position 4 (replaces beta2) in alphabetaepsilon (alpha1-beta2-alpha1-epsilon-beta2) receptors. In both cases, it appears that only a single GABA binding site is present.
Bollan
Karen A
KA
Neurosciences Institute, Ninewells Medical School, University of Dundee, Dundee DD1 9SY, UK.
Baur
Roland
R
Hales
Tim G
TG
Sigel
Erwin
E
Connolly
Christopher N
CN
D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D009865:Oocytes; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
C546274:GABRE protein, human; C546277:Gabre protein, mouse; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid