α7β2 Nicotinic Acetylcholine Receptors Assemble Function And Are Activated Primarily Via Their α7-α7 Interfaces
Department
neurobiology
Document Type
Article
Abstract
We investigated assembly and function of nicotinic acetylcholine receptors (nAChRs) composed of α7 and β2 subunits. We measured optical and electrophysiological properties of wildtype and mutant subunits expressed in cell lines and Xenopus laevis oocytes. Laser scanning confocal microscopy indicated that fluorescently tagged α7 and β2 subunits colocalize. Förster resonance energy transfer between fluorescently tagged subunits strongly suggested that α7 and β2 subunits coassemble. Total internal reflection fluorescence microscopy revealed that assemblies localized to filopodia-like processes of SH-EP1 cells. Gain-of-function α7 and β2 subunits confirmed that these subunits coassemble within functional receptors. Moreover, α7β2 nAChRs composed of wild-type subunits or fluorescently tagged subunits had pharmacological properties similar to those of α7 nAChRs, although amplitudes of α7β2 nAChR-mediated, agonist-evoked currents were generally ∼2-fold lower than those for α7 nAChRs. It is noteworthy that α7β2 nAChRs displayed sensitivity to low concentrations of the antagonist dihydro-β-erythroidine that was not observed for α7 nAChRs at comparable concentrations. In addition, cysteine mutants revealed that the α7-β2 subunit interface does not bind ligand in a functionally productive manner, partly explaining lower α7β2 nAChR current amplitudes and challenges in identifying the function of native α7β2 nAChRs. On the basis of our findings, we have constructed a model predicting receptor function that is based on stoichiometry and position of β2 subunits within the α7β2 nAChRs. Copyright © 2012 The American Society for Pharmacology and Experimental Therapeutics.
Publication Date
2-1-2012
Publication Title
Molecular Pharmacology
ISSN
0026895X
Volume
81
Issue
2
First Page
175
Last Page
188
Digital Object Identifier (DOI)
10.1124/mol.111.074088
Recommended Citation
Murray, Teresa A.; Bertrand, Daniel; Papke, Roger L.; George, Andrew A.; Pantoja, Rigo; Srinivasan, Rahul; Liu, Qiang; Wu, Jie; Whiteaker, Paul; Lester, Henry A.; and Lukas, Ronald J., "α7β2 Nicotinic Acetylcholine Receptors Assemble Function And Are Activated Primarily Via Their α7-α7 Interfaces" (2012). Translational Neuroscience. 74.
https://scholar.barrowneuro.org/neurobiology/74