| First Author | Murray TA | Year | 2012 |
| Journal | Mol Pharmacol | Volume | 81 |
| Issue | 2 | Pages | 175-88 |
| PubMed ID | 22039094 | Mgi Jnum | J:314378 |
| Mgi Id | MGI:6810690 | Doi | 10.1124/mol.111.074088 |
| Citation | Murray TA, et al. (2012) alpha7beta2 nicotinic acetylcholine receptors assemble, function, and are activated primarily via their alpha7-alpha7 interfaces. Mol Pharmacol 81(2):175-88 |
| abstractText | We investigated assembly and function of nicotinic acetylcholine receptors (nAChRs) composed of alpha7 and beta2 subunits. We measured optical and electrophysiological properties of wild-type and mutant subunits expressed in cell lines and Xenopus laevis oocytes. Laser scanning confocal microscopy indicated that fluorescently tagged alpha7 and beta2 subunits colocalize. Forster resonance energy transfer between fluorescently tagged subunits strongly suggested that alpha7 and beta2 subunits coassemble. Total internal reflection fluorescence microscopy revealed that assemblies localized to filopodia-like processes of SH-EP1 cells. Gain-of-function alpha7 and beta2 subunits confirmed that these subunits coassemble within functional receptors. Moreover, alpha7beta2 nAChRs composed of wild-type subunits or fluorescently tagged subunits had pharmacological properties similar to those of alpha7 nAChRs, although amplitudes of alpha7beta2 nAChR-mediated, agonist-evoked currents were generally ~2-fold lower than those for alpha7 nAChRs. It is noteworthy that alpha7beta2 nAChRs displayed sensitivity to low concentrations of the antagonist dihydro-beta-erythroidine that was not observed for alpha7 nAChRs at comparable concentrations. In addition, cysteine mutants revealed that the alpha7-beta2 subunit interface does not bind ligand in a functionally productive manner, partly explaining lower alpha7beta2 nAChR current amplitudes and challenges in identifying the function of native alpha7beta2 nAChRs. On the basis of our findings, we have constructed a model predicting receptor function that is based on stoichiometry and position of beta2 subunits within the alpha7beta2 nAChRs. |
