CHRNA6

Cholinergic receptor, nicotinic, alpha 6, also known as nAChRα6, is a protein that in humans is encoded by the CHRNA6 gene.^[5] The CHRNA6 gene codes for the α6 nicotinic receptor subunit that is found in certain types of nicotinic acetylcholine receptors found primarily in the brain.

CHRNA6
Identifiers
Aliases	CHRNA6, CHNRA6, cholinergic receptor nicotinic alpha 6 subunit
External IDs	OMIM: 606888; MGI: 106213; HomoloGene: 20888; GeneCards: CHRNA6; OMA:CHRNA6 - orthologs
Gene ___location (Human) Chr. Chromosome 8 (human)[1] Band 8p11.21 Start 42,752,620 bp[1] End 42,796,392 bp[1]
Gene ___location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 A2 Start 27,893,240 bp[2] End 27,903,972 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle tibialis anterior muscle mucosa of ileum gonad cerebellar cortex deltoid muscle cerebellar hemisphere prefrontal cortex right hemisphere of cerebellum substantia nigra Top expressed in lumbar spinal ganglion neural layer of retina substantia nigra ventral tegmental area blastocyst central gray substance of midbrain Ileal epithelium superior colliculus pituitary gland embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function acetylcholine binding acetylcholine receptor activity ion channel activity extracellular ligand-gated ion channel activity ligand-gated ion channel activity protein binding acetylcholine-gated cation-selective channel activity transmembrane signaling receptor activity Cellular component integral component of membrane postsynaptic membrane membrane synapse cell junction plasma membrane acetylcholine-gated channel complex dopaminergic synapse integral component of postsynaptic membrane integral component of presynaptic membrane integral component of plasma membrane neuron projection Biological process regulation of dopamine secretion response to nicotine membrane depolarization synaptic transmission, cholinergic ion transport neuromuscular synaptic transmission signal transduction chemical synaptic transmission regulation of postsynaptic membrane potential excitatory postsynaptic potential cation transmembrane transport ion transmembrane transport regulation of synaptic vesicle exocytosis regulation of membrane potential nervous system process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8973 11440 Ensembl ENSG00000147434 ENSMUSG00000031491 UniProt Q15825 Q9R0W9 RefSeq (mRNA) NM_004198 NM_001199279 NM_021369 RefSeq (protein) NP_001186208 NP_004189 NP_067344 Location (UCSC) Chr 8: 42.75 – 42.8 Mb Chr 8: 27.89 – 27.9 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Tissue distribution

α6-containing nicotinic acetylcholine receptors (nAChRs) show a restricted expression pattern in the brain. Neural nicotinic acetylcholine receptors containing α6 subunits are expressed on dopamine-releasing neurons in the midbrain.^[6][7]

Function

These receptors play a key role in regulating dopaminergic neurotransmission. Dopamine release following activation of these neurons is thought to be involved in the addictive properties of nicotine.^[8][9][10] In addition to nicotine, research in animals has implicated α6-containing nAChRs in the abusive and addictive properties of ethanol, with mecamylamine demonstrating a potent ability to block these properties.

Clinical significance

Because of their selective distribution and role in dopamine regulation, α6-containing receptors have been investigated as therapeutic targets. Due to their selective localisation on dopaminergic neurons, α6-containing nACh receptors have also been suggested as a possible therapeutic target for the treatment of Parkinson's disease.^[11][12]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.^{[§ 1]}

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|alt=Nicotine Activity on Dopaminergic Neurons edit]]

Nicotine Activity on Dopaminergic Neurons edit

1. The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602".

See also

• Nicotinic acetylcholine receptor

References

1. GRCh38: Ensembl release 89: ENSG00000147434 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031491 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: CHRNA6 cholinergic receptor, nicotinic, alpha 6".
6. Le Novère N, Zoli M, Changeux JP (November 1996). "Neuronal nicotinic receptor alpha 6 subunit mRNA is selectively concentrated in catecholaminergic nuclei of the rat brain". The European Journal of Neuroscience. 8 (11): 2428–2439. doi:10.1111/j.1460-9568.1996.tb01206.x. PMID 8950106. S2CID 23102912.
7. Meyer EL, Yoshikami D, McIntosh JM (June 2008). "The neuronal nicotinic acetylcholine receptors alpha 4* and alpha 6* differentially modulate dopamine release in mouse striatal slices". Journal of Neurochemistry. 105 (5): 1761–1769. doi:10.1111/j.1471-4159.2008.05266.x. PMC 2527994. PMID 18248619.
8. Calabresi P, Di Filippo M (October 2008). "ACh/dopamine crosstalk in motor control and reward: a crucial role for alpha 6-containing nicotinic receptors?". Neuron. 60 (1): 4–7. doi:10.1016/j.neuron.2008.09.031. PMID 18940582. S2CID 10537163.
9. Drenan RM, Grady SR, Whiteaker P, McClure-Begley T, McKinney S, Miwa JM, et al. (October 2008). "In vivo activation of midbrain dopamine neurons via sensitized, high-affinity alpha 6 nicotinic acetylcholine receptors". Neuron. 60 (1): 123–136. doi:10.1016/j.neuron.2008.09.009. PMC 2632732. PMID 18940593.
10. Exley R, Clements MA, Hartung H, McIntosh JM, Cragg SJ (August 2008). "Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens". Neuropsychopharmacology. 33 (9): 2158–2166. doi:10.1038/sj.npp.1301617. PMID 18033235.
11. Quik M, McIntosh JM (February 2006). "Striatal alpha6* nicotinic acetylcholine receptors: potential targets for Parkinson's disease therapy". The Journal of Pharmacology and Experimental Therapeutics. 316 (2): 481–489. doi:10.1124/jpet.105.094375. PMID 16210393. S2CID 20050682.
12. Bordia T, Grady SR, McIntosh JM, Quik M (July 2007). "Nigrostriatal damage preferentially decreases a subpopulation of alpha6beta2* nAChRs in mouse, monkey, and Parkinson's disease striatum". Molecular Pharmacology. 72 (1): 52–61. doi:10.1124/mol.107.035998. PMID 17409284. S2CID 25281990.

Further reading

• Zeiger JS, Haberstick BC, Schlaepfer I, Collins AC, Corley RP, Crowley TJ, et al. (March 2008). "The neuronal nicotinic receptor subunit genes (CHRNA6 and CHRNB3) are associated with subjective responses to tobacco". Human Molecular Genetics. 17 (5): 724–734. doi:10.1093/hmg/ddm344. PMID 18055561.
• Shi J, Hattori E, Zou H, Badner JA, Christian SL, Gershon ES, et al. (September 2007). "No evidence for association between 19 cholinergic genes and bipolar disorder". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 144B (6): 715–723. doi:10.1002/ajmg.b.30417. PMC 2576477. PMID 17373692.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
• Keiger CJ, Case LD, Kendal-Reed M, Jones KR, Drake AF, Walker JC (January 2003). "Nicotinic cholinergic receptor expression in the human nasal mucosa". The Annals of Otology, Rhinology, and Laryngology. 112 (1): 77–84. doi:10.1177/000348940311200115. PMID 12537063. S2CID 24705718.
• Ebihara M, Ohba H, Ohno SI, Yoshikawa T (September 2002). "Genomic organization and promoter analysis of the human nicotinic acetylcholine receptor alpha6 subunit (CHNRA6) gene: Alu and other elements direct transcriptional repression". Gene. 298 (1): 101–108. doi:10.1016/S0378-1119(02)00925-3. PMID 12406580.
• Graham A, Court JA, Martin-Ruiz CM, Jaros E, Perry R, Volsen SG, et al. (2002). "Immunohistochemical localisation of nicotinic acetylcholine receptor subunits in human cerebellum". Neuroscience. 113 (3): 493–507. doi:10.1016/S0306-4522(02)00223-3. PMID 12150770. S2CID 39839166.
• Elliott KJ, Ellis SB, Berckhan KJ, Urrutia A, Chavez-Noriega LE, Johnson EC, et al. (1997). "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". Journal of Molecular Neuroscience. 7 (3): 217–228. doi:10.1007/BF02736842. PMID 8906617. S2CID 45737923.

External links

• CHRNA6+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human CHRNA6 genome ___location and CHRNA6 gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public ___domain.