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α6

Family: Nicotinic acetylcholine receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Tissue Distribution
Physiological Consequences of Altering Gene Expression
References
Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 494 8p11.21 CHRNA6 cholinergic receptor, nicotinic, alpha 6 (neuronal) 4
Mouse 4 494 8 A3 Chrna6 cholinergic receptor, nicotinic, alpha polypeptide 6 2
Rat 4 493 16q12.3 Chrna6 cholinergic receptor, nicotinic, alpha 6 (neuronal)
Previous and Unofficial Names
cholinergic receptor, nicotinic, alpha polypeptide 6
acetylcholine receptor, nicotinic, alpha 6 (neuronal)
cholinergic receptor, nicotinic, alpha 6
neuronal acetylcholine receptor subunit alpha-6
Acra6
alpha6 nAChR
Database Links
ChEMBL Target 12774 (Hs), 102460 (Mm), 10634 (Rn)
Ensembl ENSG00000147434 (Hs), ENSMUSG00000031491 (Mm), ENSRNOG00000012283 (Rn)
Entrez Gene 8973 (Hs), 11440 (Mm), 81721 (Rn)
GeneCards CHRNA6 (Hs)
GenitoUrinary Development Molecular Anatomy Project Chrna6 (Mm)
HomoloGene 20888
Human Protein Reference Database 06056 (Hs)
InterPro Q15825 (Hs), Q9R0W9 (Mm), P43143 (Rn)
KEGG Gene hsa:8973 (Hs), mmu:11440 (Mm), rno:81721 (Rn)
OMIM 606888 (Hs)
PharmGKB Gene PA26492 (Hs)
PhosphoSitePlus Q15825 (Hs), Q9R0W9 (Mm)
Protein Ontology (PRO) PRO:000005459 (Hs)
RefSeq Nucleotide NM_004198 (Hs), NM_021369 (Mm), NM_057184 (Rn)
RefSeq Protein NP_004189 (Hs), NP_067344 (Mm), NP_476532 (Rn)
TreeFam ENSG00000147434 (Hs), ENSMUSG00000031491 (Mm), ENSRNOG00000012283 (Rn)
UniGene Hs. 103128 (Hs)
UniProt Q15825 (Hs), Q9R0W9 (Mm), P43143 (Rn)
Wikipedia α6
Nicotinic acetylcholine receptors
Search for 3D structures on the PDB
Search by keyword: Nicotinic acetylcholine receptors α6 Search by accession number: Q9R0W9, P43143, Q15825
Natural/Endogenous Ligand(s)
acetylcholine
Commonly used antagonists (Human)
α6/α3β2β3 chimera: DHβE (IC50 = 1.1 μM)
Tissue Distribution
Brain:-
Comparison of wild-type and α6 knockout mice identify α6-containing nAChRs in the striatum and retinal terminal fields
Species:  Mouse
Technique:  Radioligand binding and immunoprecipitation
References:  1
Brain:-
Expression of α6 mRNA in mouse brain is very similar to that described in rat brain. with high levels in the substantia nigra, ventral tegmental area and locus coeruleus.
Expression level:  High
Species:  Mouse
Technique:  in situ hybridisation
References:  2
Brain:-
Comparison of the binding profiles of [3H]-cytisine, [3H]-epibatidine, and [3H]-nicotine in wild-type and α6 knockout mice reveal that the binding of all three ligands in α6 Ko mice is decreased in the retina, superior colliculus and nucleus geniculate lateralis. Decrease in [3H]-epibatidine binding in ventral tegmental area and caudate-putamen nuclei was observed when binding was performed in presence of 50 nM cytisine to block the binding of [3H]-epibatidine to the widely expressed striatal α4β2 subtype. In α6 knockout mice, the high affinity binding of [125I] α-conotoxinMII is eliminated from the visual system (retina, superior colliculus and nucleus geniculate lateralis) and from the mesostriatal dopaminergic system, which includes substantia nigra-ventral tegmental area neurons and their projecting structures (nucleus accumbens and caudate putamen).
Species:  Mouse
Technique:  radioligand binding
References:  2
Brain:-
α6 mRNA is expressed in the substantia nigra and locus coeruleus ( little detectable expression in other brain structures).
Expression level:  High
Species:  Rat
Technique:  in situ hybridisation
References:  6
Tissue Distribution Comments
Using in situ hybridisation research reveals that in rhesus monkey (Macaca mulatta) and squirrel monkey (Saimiri sciureus) the α6 mRNA distribution in brain is similar to rodents:- high levels in substantia nigra, ventral tegmental area, locus coeruleu, medial habenula[5,7]
Physiological Consequences of Altering Gene Expression
Knockout mice do not display any gross neurological or behavioural deficits but lack α-conotoxin MII binding sites in the brain.
Species:  Mouse
Tissue:  in vivo
Technique:  knockout
References:  2
Transgenic mice expressing α6 containing an L9’S substitution in the second transmembrane domain display extremely high activity during their active cycle in the dark. Mice also display locomotor activation following injection of low nicotine doses. Neurons in the ventral tegmental area are very sensitive to activation by nicotine. Enhanced response is observed for dopaminergic neurons. Synaptosomal dopamine release in striatal or olfactory tubercle preparations stimulated by nicotine is altered.
Species:  Mouse
Tissue: 
Technique:  Transgenesis
References:  3

REFERENCES

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1. Champtiaux, N; Gotti, C; Cordero-Erausquin, M; David, DJ; Przybylski, C; Léna, C; Clementi, F; Moretti, M; Rossi, FM; Le Novère, N; et al.. (2003) Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice. J. Neurosci., 23 (21): 7820-9. [PMID:12944511]

2. Champtiaux, N; Han, ZY; Bessis, A; Rossi, FM; Zoli, M; Marubio, L; McIntosh, JM; Changeux, JP. (2002) Distribution and pharmacology of alpha 6-containing nicotinic acetylcholine receptors analyzed with mutant mice. J. Neurosci., 22 (4): 1208-17. [PMID:11850448]

3. Drenan, RM; Grady, SR; Whiteaker, P; McClure-Begley, T; McKinney, S; Miwa, JM; Bupp, S; Heintz, N; McIntosh, JM; Bencherif, M; et al.. (2008) In vivo activation of midbrain dopamine neurons via sensitized, high-affinity alpha 6 nicotinic acetylcholine receptors. Neuron, 60 (1): 123-36. [PMID:18940593]

4. Elliott, KJ; Ellis, SB; Berckhan, KJ; Urrutia, A; Chavez-Noriega, LE; Johnson, EC; Veliçelebi, G; Harpold, MM. (1996) Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits. J. Mol. Neurosci., 7 (3): 217-28. [PMID:8906617]

5. Han, ZY; Le Novère, N; Zoli, M; Hill, JA; Champtiaux, N; Changeux, JP. (2000) Localization of nAChR subunit mRNAs in the brain of Macaca mulatta. Eur. J. Neurosci., 12 (10): 3664-74. [PMID:11029636]

6. Le Novère, N; Zoli, M; Changeux, JP. (1996) Neuronal nicotinic receptor alpha 6 subunit mRNA is selectively concentrated in catecholaminergic nuclei of the rat brain. Eur. J. Neurosci., 8 (11): 2428-39. [PMID:8950106]

7. Quik, M; Polonskaya, Y; Gillespie, A; Jakowec, M; Lloyd, GK; Langston, JW. (2000) Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization. J. Comp. Neurol., 425 (1): 58-69. [PMID:10940942]

To cite this database page, please use the following:

Cecilia Gotti, Michael. J. Marks, Neil S. Millar, Susan Wonnacott.
Nicotinic acetylcholine receptors: α6. Last modified on 16/11/2011. Accessed on 18/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=467.


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