image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

β4

Family: Nicotinic acetylcholine receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Tissue Distribution
Physiological Consequences of Altering Gene Expression
Clinically-Relevant Mutations and Pathophysiology
References
Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 498 15q24 CHRNB4 cholinergic receptor, nicotinic, beta 4 (neuronal) 7
Mouse 4 495 9 B Chrnb4 cholinergic receptor, nicotinic, beta polypeptide 4 3
Rat 4 495 8q24 Chrnb4 cholinergic receptor, nicotinic, beta 4 (neuronal) 2
Previous and Unofficial Names
cholinergic receptor, nicotinic, beta polypeptide 4
acetylcholine receptor, nicotinic, beta 4 (neuronal)
Acetylcholine receptor beta 4
N-alpha 2
cholinergic receptor, nicotinic, beta 4
neuronal acetylcholine receptor non-alpha-2 chain
neuronal acetylcholine receptor subunit beta-4
Acrb-4
Acrb4
Database Links
ChEMBL Target 10645 (Hs), 12717 (Rn)
Ensembl ENSG00000117971 (Hs), ENSMUSG00000035200 (Mm), ENSRNOG00000014427 (Rn)
Entrez Gene 1143 (Hs), 108015 (Mm), 25103 (Rn)
GeneCards CHRNB4 (Hs)
GenitoUrinary Development Molecular Anatomy Project Chrnb4 (Mm)
HomoloGene 20196
Human Protein Reference Database 00337 (Hs)
InterPro P30926 (Hs), Q8R493 (Mm), P12392 (Rn)
KEGG Gene hsa:1143 (Hs), mmu:108015 (Mm), rno:25103 (Rn)
OMIM 118509 (Hs)
PharmGKB Gene PA26496 (Hs)
PhosphoSitePlus P30926 (Hs), Q8R493 (Mm), P12392 (Rn)
Protein Ontology (PRO) PRO:000005465 (Hs)
RefSeq Nucleotide NM_000750 (Hs), NM_148944 (Mm), NM_052806 (Rn)
RefSeq Protein NP_000741 (Hs), NP_683746 (Mm), NP_434693 (Rn)
TreeFam ENSG00000117971 (Hs), ENSMUSG00000035200 (Mm), ENSRNOG00000014427 (Rn)
UniGene Hs. 624178 (Hs)
UniProt P30926 (Hs), Q8R493 (Mm), P12392 (Rn)
Wikipedia β4
Nicotinic acetylcholine receptors
Search for 3D structures on the PDB
Search by keyword: Nicotinic acetylcholine receptors β4 Search by accession number: P12392, Q8R493, P30926
Natural/Endogenous Ligand(s)
acetylcholine
Tissue Distribution
Brain: medial habenula, mitral cell layer and the accessory olfactory bulb, interpeduncular nucleus, inferior colliculus and the medial vestibular nucleus ( mRNA restricted to relatively few nuclei)
Expression level:  High
Species:  Mouse
Technique:  Radioligand binding
References:  13
Brain: medial habenula, cerebral cortex, hippocampus, motor trigeminal nucleus, locus coreulus, cerebellum, interpeduncular nucleus (no expression in thalamus).
Expression level:  High
Species:  Rat
Technique:  in situ hybridisation
References:  2
Tissue Distribution Comments
Deletion of β4 subunit in knockout mice has little effect on total [3H]- or [125I]-epibatidine binding with the exception of a partial reduction in the signal intensity in the fasiculus retroflexus, interpeduncular nucleus and the inferior colliculus. The effects of β4 gene deletion were more readily observable when cytisine was included in the incubation with [3H]- or [125I]-epibatidine. Under these experimental conditions, robust effects could be observed in the medial habenula, the fasiculus retroflexis, the interpeducular nucleus and the inferior colliculus, all of which expressed high levels of cytisine-resistant [125I]epibatidine binding [1,10].

Expression of β4 mRNA in rhesus monkey (Macaca Mulatta) brain is similar to that described in rodents. High expression is detected in thalamic nuclei, substantia nigra pars compacta and vertral tegmental area. Expression is also detected in cortex (layer VI showing the highest level of expression) and lower levles in hippocampus and caudate[4].

Expression of β4 mRNA in suirrel monkey (Samimiri sciureus) appears to differ from that in rodents or macaques. High levels of expression brain have been detected in caudate, putamen and hippocampus. However, compared to expression levels in the cotex, levels of expression were relatively low in thalamic nuclei, substantia nigra pars compacta and medial habenula[6].
Physiological Consequences of Altering Gene Expression
Knockout mice display reduced acetylcholine-activated whole-cell currents in superior cervical ganglion neurons; autonomic cardiac and intestinal dysfunction are also observed; decreased anxiety-related responses; resistance to nicotine-induced seizures; decreased nicotine withdrawal. Expression of α3 subunit mRNA is greatly reduced in the mitral cell layer of the olfactory bulb, and the inferior and the superior colliculus of β4 knockout mice.
Species:  Mouse
Tissue:  in vivo
Technique:  Gene knockout
References:  5,9,11-12,14
Clinically-Relevant Mutations and Pathophysiology
Disease:  Sporadic amyotrophic lateral sclerosis
References:  8
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human multiple 8

REFERENCES

Show »

1. Baddick C.G. and Marks M.J. (2011) An auroradiographic survey of mouse brain nicotinic acetylcholine receptors defined by null mutants. Biochem. Pharmacol.,, . [PMID:21575611]

2. Duvoisin, RM; Deneris, ES; Patrick, J; Heinemann, S. (1989) The functional diversity of the neuronal nicotinic acetylcholine receptors is increased by a novel subunit: beta 4. Neuron, 3 (4): 487-96. [PMID:2642007]

3. Eng, CM; Kozak, CA; Beaudet, AL; Zoghbi, HY. (1991) Mapping of multiple subunits of the neuronal nicotinic acetylcholine receptor to chromosome 15 in man and chromosome 9 in mouse. Genomics, 9 (2): 278-82. [PMID:2004777]

4. 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]

5. Kedmi, M; Beaudet, AL; Orr-Urtreger, A. (2004) Mice lacking neuronal nicotinic acetylcholine receptor beta4-subunit and mice lacking both alpha5- and beta4-subunits are highly resistant to nicotine-induced seizures. Physiol. Genomics, 17 (2): 221-9. [PMID:14996991]

6. 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]

7. Raimondi, E; Rubboli, F; Moralli, D; Chini, B; Fornasari, D; Tarroni, P; De Carli, L; Clementi, F. (1992) Chromosomal localization and physical linkage of the genes encoding the human alpha 3, alpha 5, and beta 4 neuronal nicotinic receptor subunits. Genomics, 12 (4): 849-50. [PMID:1572664]

8. Sabatelli, M; Eusebi, F; Al-Chalabi, A; Conte, A; Madia, F; Luigetti, M; Mancuso, I; Limatola, C; Trettel, F; Sobrero, F; et al.. (2009) Rare missense variants of neuronal nicotinic acetylcholine receptor altering receptor function are associated with sporadic amyotrophic lateral sclerosis. Hum. Mol. Genet., 18 (20): 3997-4006. [PMID:19628475]

9. Salas, R; Cook, KD; Bassetto, L; De Biasi, M. (2004) The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice. Neuropharmacology, 47 (3): 401-7. [PMID:15275829]

10. Salas, R; Pieri, F; De Biasi, M. (2004) Decreased signs of nicotine withdrawal in mice null for the beta4 nicotinic acetylcholine receptor subunit. J. Neurosci., 24 (45): 10035-9. [PMID:15537871]

11. Salas, R; Pieri, F; Fung, B; Dani, JA; De Biasi, M. (2003) Altered anxiety-related responses in mutant mice lacking the beta4 subunit of the nicotinic receptor. J. Neurosci., 23 (15): 6255-63. [PMID:12867510]

12. Wang, N; Orr-Urtreger, A; Chapman, J; Rabinowitz, R; Korczyn, AD. (2003) Deficiency of nicotinic acetylcholine receptor beta 4 subunit causes autonomic cardiac and intestinal dysfunction. Mol. Pharmacol., 63 (3): 574-80. [PMID:12606764]

13. Whiteaker, P; Jimenez, M; McIntosh, JM; Collins, AC; Marks, MJ. (2000) Identification of a novel nicotinic binding site in mouse brain using [(125)I]-epibatidine. Br. J. Pharmacol., 131 (4): 729-39. [PMID:11030722]

14. Xu, C; Lu, Y; Tang, G; Wang, R. (1999) Expression of voltage-dependent K(+) channel genes in mesenteric artery smooth muscle cells. Am. J. Physiol., 277 (5 Pt 1): G1055-63. [PMID:10564112]

To cite this database page, please use the following:

Cecilia Gotti, Michael. J. Marks, Neil S. Millar, Susan Wonnacott.
Nicotinic acetylcholine receptors: β4. Last modified on 07/11/2011. Accessed on 22/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=474.


Contact us | Print | Back to top | Help