Role of two acetylcholine receptor subunit domains in homomer formation and intersubunit recognition, as revealed by alpha 3 and alpha 7 subunit chimeras.
Differential expression of subunit genes from the nicotinic acetylcholine receptor (AChR) superfamily yields distinct receptor subtypes. As each AChR subtype has a specific subunit composition and many subunit combinations appear not to be expressed, each subunit must contain some information leading to proper assembly. The neuronal AChR subunits alpha 3 and alpha 7 are expressed in bovine chromaffin cells, probably as constituents of two different AChR subtypes. These subunits have different assembly behavior when expressed in heterologous expression systems: alpha 7 subunits are able to produce homomeric AChRs, whereas alpha 3 subunits require other "structural" subunits for functional expression of AChRs. This feature allows the dissection of the requirements for subunit interactions during AChR formation. Analysis of alpha 7/alpha 3 chimeric constructs identified two regions essential to homomeric assembly and intersubunit recognition: an N-terminal extracellular region, controlling the initial association between subunits, and a second domain within a region comprising the first putative transmembrane segment, M1, and the cytoplasmic loop coupling it to the pore-forming segment, M2, involved in the subsequent interaction and stabilization of the oligomeric complex.
García-Guzmán
M
M
Department of Neurochemistry, University of Alicante, Spain.
Sala
F
F
Sala
S
S
Campos-Caro
A
A
Criado
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014162:Transfection; D014981:Xenopus
D002038:Bungarotoxins; D046911:Macromolecular Substances; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins