Alpha7 nicotinic acetylcholine receptor upregulation by anti-apoptotic Bcl-2 proteins

α7 nicotinic acetylcholine receptor (α7 nAChR) assembly and surface expression increase when cells express anti-apoptotic Bcl-2 family proteins. The study uses recombinant expression of α7 nAChRs with the essential chaperone NACHO and genome-wide cDNA library screening to identify Bcl-2 members that enhance receptor assembly and functional cell surface display. Mechanistically, the effects depend on an intracellular motif in α7 that resembles the BH3 binding domain of pro-apoptotic Bcl-2 proteins, and they can be blocked by BH3 mimetic Bcl-2 inhibitors. Overexpression of Mcl-1 increases surface expression of endogenous α7 receptors in neurons, and combining chemotherapeutic Bcl-2 inhibitors suppresses α7 receptor assembly, linking α7 biogenesis to cell survival pathways.