Alpha 3, alpha 5, and beta 4: three members of the rat neuronal nicotinic acetylcholine receptor-related gene family form a gene cluster.
Open accessAbstract
We have identified two additional members of the neuronal nicotinic acetylcholine receptor (nAChR)-related gene family. cDNA clones for one new gene, designated alpha 5, were isolated from rat hippocampus and rat PC12 cell line cDNA libraries. The alpha 5 gene encodes a protein of 48,800 daltons (424 amino acids) which exhibits significant overall amino acid sequence identity with the previously cloned rat nAChR subunits alpha 1 (49%), alpha 2 (55%), alpha 3 (52%), and alpha 4 (49%). Features characteristic of other nAChR alpha-subunits are present such as conserved cysteine residues at positions 127, 141, 191, and 192, and four strongly hydrophobic domains. A second addition to the nAChR-related gene family, designated beta 4, is encoded in overlapping rat genomic clones lambda DD15 and lambda RG518A. The beta 4 gene, encoding a mature protein of 53,300 daltons (475 amino acids), consists of 6 exons and has a transcription unit length of approximately 18 kilobase pairs. The beta 4 gene encoded protein shows considerable amino acid sequence identity with nAChR beta 1 (43%), beta 2 (64%), and beta 3 (44%) subunits. Northern blots showed that, along with alpha 3 and beta 2, transcripts for both the alpha 5 and beta 4 genes are present in the PC12 cell line, while in situ hybridization experiments demonstrated expression of the alpha 5 and beta 4 genes in a small number of nuclei in the central nervous system. Finally, the genes that encode the beta 4, alpha 3, and alpha 5 proteins are transcribed with convergent polarities and form a tightly linked gene cluster spanning approximately 60 kilobase pairs.
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Mice heterozygous for the α3 subunit show attenuated nicotine-induced seizures, and α3 lies in the same gene cluster as α5 and β4.
“Attenuation of nicotine-induced seizure is also present in mice heterozygous for the α3 subunit, which is found in the same gene cluster that contains α5 and β4 (Boulter et al. 1990, Salas et al. 2004a).”
From Reward, addiction, withdrawal to nicotine (2011) · cites this paper as Boulter et al. 1990
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- Authors
- Boulter, J., O'Shea-Greenfield, A., Duvoisin, R. M., Connolly, J. G., Wada, E., Jensen, A., Gardner, P. D., Ballivet, M., Deneris, E. S., & McKinnon, D.
- Affiliations
- Salk Institute for Biological Studies (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1990-03
- Volume
- 265
- Issue
- 8
- Pages
- 4472-4482
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1556409059
- Cited by
- 302
- References
- 49
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 1 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 7 · 2013: 6 · 2012: 2
- FWCI
- 10.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- neuronal nicotinic acetylcholine receptors, gene clusters, convergent transcription, cDNA cloning, gene structure, amino acid sequence identity, hippocampus, PC12 cells, central nervous system expression, rats
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Brain Chemistry, DNA, Multigene Family, Hippocampus, Molecular Sequence Data, Neurons, Nucleic Acid Hybridization, Pheochromocytoma, Receptors, Nicotinic, RNA, Tissue Distribution, Transcription, Genetic, Tumor Cells, Cultured, Restriction Mapping, Gene Expression, Macromolecular Substances, Rats
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