THE ALPHA-5-GENE PRODUCT ASSEMBLES WITH MULTIPLE ACETYLCHOLINE-RECEPTOR SUBUNITS TO FORM DISTINCTIVE RECEPTOR SUBTYPES IN BRAIN

The acetylcholine receptor (AChR) alpha5 gene has been classified as a member of the AChR gene family based on sequence homology. Expression studies, however, have yet to identify a function for the alpha5 gene product or even to demonstrate an interaction with known AChR subunits. We report here that the alpha5 gene product is identical to the 49 kd protein previously found on immunoblots of AChRs purified from brain and ciliary ganglia. In brain the alpha5 gene product is present both in alpha3- and in alpha4-based receptor subtypes, while in the ganglion it is found in an alpha3-based receptor subtype concentrated in postsynaptic membrane. Immunoprecipitation experiments with subunit-specific monoclonal antibodies indicate that some native AChRs are likely to have at least three kinds of subunits, with two being of the alpha type. These findings support new views about the construction of AChRs in neurons.