Nicotinic receptor assembly requires multiple regions throughout the gamma subunit.
Assembly of ionotropic neurotransmitter receptors typified by acetylcholine receptors (AChRs) is thought to be directed by an N-terminal extracellular domain of a subunit. Consistent with this hypothesis, chimeras with the delta subunit N-terminal domain fused to the rest of the gamma subunit can substitute for delta, but not gamma, subunits during AChR assembly. However, chimeras with the gamma subunit N-terminal domain fused to the rest of the delta subunit cannot substitute for gamma or delta subunits during assembly. Furthermore, expression of this chimera with the four wild-type subunits prevents the formation of alpha-bungarotoxin (Bgt) binding sites. Instead of AChR pentamers, complexes are assembled containing only the chimera and either alpha or beta subunits. Based on the results of additional gamma-delta chimeras, there are at least two different regions within the C-terminal half of the chimera required for the dominant-negative effect. Our results indicate that the N-terminal domain of the gamma subunit mediates the initial subunit associations, whereas signals in the C-terminal half of the subunit are required for subsequent subunit interactions.
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Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, Illinois 60637, USA.
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D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002038:Bungarotoxins / Q000378:metabolism; D002460:Cell Line; D002678:Chimera / Q000235:genetics / Q000502:physiology; D010446:Peptide Fragments / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D011499:Protein Processing, Post-Translational; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014101:Torpedo
D002038:Bungarotoxins; D010446:Peptide Fragments; D020033:Protein Isoforms; D011978:Receptors, Nicotinic