title: The nicotinic α5 subunit can replace either an acetylcholine-binding or nonbinding subunit in the α4β2* neuronal nicotinic receptor.
abstract: Heteropentameric neuronal nicotinic receptors assemble so that the canonical acetylcholine-binding sites are located at the interfaces between two pairs of subunits, while the fifth subunit does not participate in a canonical transmitter-binding site. Several subunits are considered to be unable to participate in forming a functional receptor when they occupy a position that would contribute to such a site, including the α5 subunit. The α5 subunit is of interest because of its apparent involvement in nicotine dependence and in the control of dopamine release. We have examined this question using α4 and β2 subunits in concatemeric constructs with the α5 subunit, expressed in Xenopus oocytes. Using dimeric constructs of α4 and β2 subunits expressed with free α5 and pentameric constructs incorporating a single copy of α5, we find that the α5 subunit can occupy the position of a nonbinding subunit, or replace a β2 subunit participating in a canonical binding site. The resulting receptors functionally resemble pentamers assembled with two copies of α4 and three copies of β2. Functional receptors apparently cannot be formed with α5 subunits in both canonical binding sites. These observations extend the present ideas on the possible positions in the pentamer that may be occupied by the α5 subunit, and suggest that additional physiologic or pharmacological subtypes of neuronal nicotinic receptors may be present in neurons.
authors.affiliation: Department of Anesthesiology and the Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, Missouri (X.J., J.H.S.); and Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, United Kingdom (I.B.).
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Jin
authors.forename: Isabel
authors.initials: I
authors.lastname: Bermudez
authors.forename: Joe Henry
authors.initials: JH
authors.lastname: Steinbach
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D005260:Female; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D055503:Protein Multimerization; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus
chemical_list: D021122:Protein Subunits; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; C577601:nicotinic receptor alpha5 subunit, human; D000109:Acetylcholine