ACETYLCHOLINE-RECEPTOR SUBUNIT HOMOMER FORMATION REQUIRES COMPATIBILITY BETWEEN AMINO-ACID-RESIDUES OF THE M1 AND M2 TRANSMEMBRANE SEGMENTS

The neuronal nicotinic acetylcholine receptor (nAChR) subunits alpha 3 and alpha 7 have different assembly behavior when expressed in hetero logous expression systems: alpha 3 subunits require other subunits to assemble functional nAChRs, whereas alpha 7 subunits can produce homom eric nAChRs. A previous analysis of alpha 7/alpha 3 chimeric construct s identified a domain comprising the first putative membrane-spanning segment, M1, as essential to homomeric assembly. The present study dis sected further this domain, identifying three amino acid residues, whi ch are located at the most intracellular third of the M1 transmembrane segment, as important in the assembly of homomers. Moreover, formatio n of homooligomeric complexes seems to require a compatible accommodat ion between this region and certain residues of the second transmembra ne segment, M2. Thus, compatibility between defined domains of the M1 and M2 transmembrane segments appears as a determinant factor governin g homomer association of nAChR subunits.