Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2011 Nov 04;28644:37905-37918. doi: 10.1074/jbc.M111.264044.
Show Gene links
Show Anatomy links
Reporter mutation studies show that nicotinic acetylcholine receptor (nAChR) α5 Subunits and/or variants modulate function of α6*-nAChR.
Dash B
,
Chang Y
,
Lukas RJ
.
???displayArticle.abstract???
To further the understanding of functional α6α5*-nicotinic acetylcholine receptors (nAChR; the asterisk (*) indicates known or possible presence of other subunits), we have heterologously expressed in oocytes different, mouse or human, nAChR subunit combinations. Coexpression with wild-type α5 subunits or chimeric α5/β3 subunits (in which the human α5 subunit N-terminal, extracellular domain is linked to the remaining domains of the human β3 subunit) almost completely abolishes the very small amount of function seen for α6β4*-nAChR and does not induce function of α6β2*-nAChR. Coexpression with human α5(V9)'(S) subunits bearing a valine 290 to serine mutation in the 9' position of the second transmembrane domain does not rescue the function of α6β4*-nAChR or induce function of α6β2*-nAChR. However, coexpression with mutant chimeric α5/β3(V9)'(S) subunits has a gain-of-function effect (higher functional expression and agonist sensitivity and spontaneous opening inhibited by mecamylamine) on α6β4*-nAChR. Moreover, N143D + M145V mutations in the α6 subunit N-terminal domain enable α5/β3(V9)'(S) subunits to have a gain-of-function effect on α6β2*-nAChR. nAChR containing chimeric α6/α3 subunits plus either β2 or β4 subunits have some function that is modulated in the presence of α5 or α5/β3 subunits. Coexpression with α5/β3(V9)'(S) subunits has a gain-of-function effect more pronounced than that in the presence of α5(V9)'(S) subunits. Gain-of-function effects are dependent, sometimes subtly, on the nature and apparently the extracellular, cytoplasmic, and/or transmembrane domain topology of partner subunits. These studies yield insight into assembly of functional α6α5*-nAChR and provide tools for development of α6*-nAChR-selective ligands that could be important in the treatment of nicotine dependence, and perhaps other neurological diseases.
Boulter,
Alpha 3, alpha 5, and beta 4: three members of the rat neuronal nicotinic acetylcholine receptor-related gene family form a gene cluster.
1990, Pubmed
Boulter,
Alpha 3, alpha 5, and beta 4: three members of the rat neuronal nicotinic acetylcholine receptor-related gene family form a gene cluster.
1990,
Pubmed
Broadbent,
Incorporation of the beta3 subunit has a dominant-negative effect on the function of recombinant central-type neuronal nicotinic receptors.
2006,
Pubmed
,
Xenbase
Brown,
Nicotinic alpha5 subunit deletion locally reduces high-affinity agonist activation without altering nicotinic receptor numbers.
2007,
Pubmed
Chang,
Substitutions of the highly conserved M2 leucine create spontaneously opening rho1 gamma-aminobutyric acid receptors.
1998,
Pubmed
,
Xenbase
Couturier,
Alpha 5, alpha 3, and non-alpha 3. Three clustered avian genes encoding neuronal nicotinic acetylcholine receptor-related subunits.
1990,
Pubmed
,
Xenbase
Cui,
The beta3 nicotinic receptor subunit: a component of alpha-conotoxin MII-binding nicotinic acetylcholine receptors that modulate dopamine release and related behaviors.
2003,
Pubmed
Dash,
Identification of N-terminal extracellular domain determinants in nicotinic acetylcholine receptor (nAChR) α6 subunits that influence effects of wild-type or mutant β3 subunits on function of α6β2*- or α6β4*-nAChR.
2011,
Pubmed
,
Xenbase
Drenan,
In vivo activation of midbrain dopamine neurons via sensitized, high-affinity alpha 6 nicotinic acetylcholine receptors.
2008,
Pubmed
Flora,
Neuronal and extraneuronal expression and regulation of the human alpha5 nicotinic receptor subunit gene.
2000,
Pubmed
Fucile,
The neuronal alpha6 subunit forms functional heteromeric acetylcholine receptors in human transfected cells.
1998,
Pubmed
Gerzanich,
"Orphan" alpha6 nicotinic AChR subunit can form a functional heteromeric acetylcholine receptor.
1997,
Pubmed
,
Xenbase
Groot-Kormelink,
Formation of functional alpha3beta4alpha5 human neuronal nicotinic receptors in Xenopus oocytes: a reporter mutation approach.
2001,
Pubmed
,
Xenbase
Kuryatov,
Human alpha6 AChR subtypes: subunit composition, assembly, and pharmacological responses.
2000,
Pubmed
,
Xenbase
Kuryatov,
Roles of accessory subunits in alpha4beta2(*) nicotinic receptors.
2008,
Pubmed
Labarca,
Channel gating governed symmetrically by conserved leucine residues in the M2 domain of nicotinic receptors.
1995,
Pubmed
,
Xenbase
Lester,
Gain of function mutants: ion channels and G protein-coupled receptors.
2000,
Pubmed
Lukas,
Neurotoxicity of channel mutations in heterologously expressed alpha7-nicotinic acetylcholine receptors.
2001,
Pubmed
Lukas,
International Union of Pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits.
1999,
Pubmed
McClure-Begley,
Acetylcholine-stimulated [3H]GABA release from mouse brain synaptosomes is modulated by alpha4beta2 and alpha4alpha5beta2 nicotinic receptor subtypes.
2009,
Pubmed
Miko,
A TM2 residue in the beta1 subunit determines spontaneous opening of homomeric and heteromeric gamma-aminobutyric acid-gated ion channels.
2004,
Pubmed
,
Xenbase
Moroni,
Non-agonist-binding subunit interfaces confer distinct functional signatures to the alternate stoichiometries of the alpha4beta2 nicotinic receptor: an alpha4-alpha4 interface is required for Zn2+ potentiation.
2008,
Pubmed
,
Xenbase
Orr-Urtreger,
Mice homozygous for the L250T mutation in the alpha7 nicotinic acetylcholine receptor show increased neuronal apoptosis and die within 1 day of birth.
2000,
Pubmed
,
Xenbase
Revah,
Mutations in the channel domain alter desensitization of a neuronal nicotinic receptor.
1991,
Pubmed
,
Xenbase
Salas,
The nicotinic acetylcholine receptor subunit alpha 5 mediates short-term effects of nicotine in vivo.
2003,
Pubmed
Treinin,
A mutated acetylcholine receptor subunit causes neuronal degeneration in C. elegans.
1995,
Pubmed
Wada,
The distribution of mRNA encoded by a new member of the neuronal nicotinic acetylcholine receptor gene family (alpha 5) in the rat central nervous system.
1990,
Pubmed
Wang,
Autonomic function in mice lacking alpha5 neuronal nicotinic acetylcholine receptor subunit.
2002,
Pubmed
Wang,
Nicotinic acetylcholine receptor alpha5 subunits modulate oxotremorine-induced salivation and tremor.
2004,
Pubmed
Winzer-Serhan,
Expression of alpha5 nicotinic acetylcholine receptor subunit mRNA during hippocampal and cortical development.
2005,
Pubmed
Yu,
Functional contribution of the alpha5 subunit to neuronal nicotinic channels expressed by chick sympathetic ganglion neurones.
1998,
Pubmed
