THE AMINO-ACID-RESIDUES-1-128 IN THE ALPHA-SUBUNIT OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR CONTAIN ASSEMBLY SIGNALS

Expression of nicotinic acetylcholine receptor (AChR) involves complex processes including assembly of different receptor subunits into hete ro-oligomers. To identify the minimal N-terminal region involved in AC hR subunit association, we used a dominant negative assay. Co-expressi on of fragments of the a subunit, containing the N-terminal extracellu lar domain and transmembrane domain 1 (TM 1), with the parental AChR s ubunits in Xenopus oocytes blocked functional expression of the recept or. In contrast, co-expression of N-terminal extracellular fragments w ithout TM1 failed to inhibit functional expression of AChRs, but alter ed the functional properties of co-expressed parental AChRs. Furthermo re, when these a subunit fragments were co-expressed with the beta, ga mma, and delta subunits, they were co-immunoprecipitated with a mixtur e of beta, gamma, and delta subunit specific antibodies. These results suggest that 'assembly signals' are confined to a local structure in the N-terminal extracellular domain. Our findings also indicate that a n assembly step may be a target for genetic intervention not only to b lock the expression of functional receptors, but also to alter the fun ction of the receptor.