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The nicotinic α5 subunit can replace either an acetylcholine-binding or nonbinding subunit in the α4β2* neuronal nicotinic receptor.

Authors
  • Jin, Xiaochun
  • Bermudez, Isabel
  • Steinbach, Joe Henry
Type
Published Article
Journal
Molecular Pharmacology
Publisher
American Society for Pharmacology & Experimental Therapeutics
Publication Date
Jan 01, 2014
Volume
85
Issue
1
Pages
11–17
Identifiers
DOI: 10.1124/mol.113.089979
PMID: 24184962
Source
Medline
License
Unknown

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.

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