ROLE OF 2 ACETYLCHOLINE-RECEPTOR SUBUNIT DOMAINS IN HOMOMER FORMATIONAND INTERSUBUNIT RECOGNITION, AS REVEALED BY ALPHA-3 AND ALPHA-7 SUBUNIT CHIMERAS

Differential expression of subunit genes from the nicotinic acetylchol ine 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 som e information leading to proper assembly. The neuronal AChR subunits a lpha 3 and alpha 7 are expressed in bovine chromaffin cells, probably as constituents of two different AChR subtypes. These subunits have di fferent assembly behavior when expressed in heterologous expression sy stems: alpha 7 subunits are able to produce homomeric AChRs, whereas a lpha 3 subunits require other ''structural'' subunits for functional e xpression of AChRs. This feature allows the dissection of the requirem ents for subunit interactions during AChR formation. Analysis of alpha 7/alpha 3 chimeric constructs identified two regions essential to hom omeric assembly and intersubunit recognition: an N-terminal extracellu lar region, controlling the initial association between subunits, and a second domain within a region comprising the first putative transmem brane segment, M1, and the cytoplasmic loop coupling it to the pore-fo rming segment, M2, involved in the subsequent interaction and stabiliz ation of the oligomeric complex.