Multiple Roles of the Conserved Key Residue Arginine 209 in Neuronal Nicotinic Receptors

摘要

We have examined the role of a highly conserved arginine (R209), which flanks the MI transmembrane segment of nAChRs, in the biogenesis and function of neuronal nAChRs. Point mutations revealed that, in a.Bgtx-sensitive neuronal (17 nAChRs, the conserved arginine is required for the transport of assembled receptors to the cell surface. By contrast, R209 does not play any role in the transport of assembled (1-Bgtx-insensitive neuronal (13{34 nAChRs to the cell surface. However, a basic residue at this position of (13 and {34 subunits is necessary for either synthesis, folding, or assembly of (13{34 receptors. Moreover, electrophysiological experiments revealed that in (13{34 receptors the conserved arginine of the (13 subunit is involved in either coupling agonist binding to the channel or regulating single channel kinetics.