Host Cell-Specific Folding and Assembly of the Neuronal Nicotinic Acetylcholine Receptor α7 Subunit
Article first published online: 18 NOV 2002
Journal of Neurochemistry
Volume 68, Issue 5, pages 2140–2151, May 1997
How to Cite
Cooper, S. T. and Millar, N. S. (1997), Host Cell-Specific Folding and Assembly of the Neuronal Nicotinic Acetylcholine Receptor α7 Subunit. Journal of Neurochemistry, 68: 2140–2151. doi: 10.1046/j.1471-4159.1997.68052140.x
- Issue published online: 18 NOV 2002
- Article first published online: 18 NOV 2002
- Received November 1, 1996; revised manuscript received December 31, 1996; accepted December 31, 1996.
- Protein folding;
- Nicotinic acetylcholine receptor
Abstract: Expression of the cloned neuronal nicotinic acetylcholine receptor (nAChR) α7 subunit in several cultured mammalian cell lines has revealed that the folding, assembly, and subcellular localization of this protein are critically dependent upon the nature of the host cell. In all cell lines that were examined, high levels of α7 protein were detected by metabolic labelling and immunoprecipitation after transfection with the cloned α7 cDNA. In contrast, elevated levels of α-bungarotoxin binding could be detected in only two of the nine cell lines. Both of these “α7-permissive” cell lines [rat phaeochromocytoma (PC12) and human neuroblastoma (SH-SY5Y)] express an endogenous α7 subunit. However, by expression of an epitope-tagged α7 subunit, it has been possible to show that the elevation in surface α-bungarotoxin binding in these two cell lines is due to expression of cDNA-encoded α7. The cell-specific misfolding of the neuronal nAChR α7 subunit is a phenomenon that is not shared by either the hetero-oligomeric muscle nAChR or the homo-oligomeric serotonin receptor 5-HT3 subunit. Our data also indicate that the cell-specific misfolding cannot be explained by a requirement for the coassembly with other known nAChR subunits and cannot be alleviated by treatments that have been reported to affect the assembly efficiency of other neurotransmitter-gated ion channels.