Biology:CHRNA7

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Neuronal acetylcholine receptor subunit alpha-7, also known as nAChRα7, is a protein that in humans is encoded by the CHRNA7 gene.[1] The protein encoded by this gene is a subunit of certain nicotinic acetylcholine receptors (nAchR).

Function

The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are thought to be hetero-pentamers composed of homologous subunits. The proposed structure for each subunit is a conserved N-terminal extracellular domain followed by three conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region. The protein encoded by this gene forms a homo-oligomeric channel, displays marked permeability to calcium ions and is a major component of brain nicotinic receptors that are blocked by, and highly sensitive to, alpha-bungarotoxin. Once this receptor binds acetylcholine, it undergoes an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. This gene is located in a region identified as a major susceptibility locus for juvenile myoclonic epilepsy and a chromosomal location involved in the genetic transmission of schizophrenia. An evolutionarily recent partial duplication event in this region results in a hybrid containing sequence from this gene and a novel FAM7A gene.[2]

Disruption of alpha-7 nicotinic receptors in schizophrenia is believed to contribute at least in part to the abnormally high prevalence of extremely heavy smoking in those affected by the disease. This observed particularly high nicotine intake compared to the average smoker is hypothesized to be a subconscious effort to activate the low-affinity alpha-7 receptors.

Interactions

CHRNA7 has been shown to interact with FYN.[3]

Gene expression

The CHRNA7 gene is primarily expressed in the posterior amygdalar nucleus and the field CA3 of Ammon's horn in the mouse, and in the mammillary body in humans. Gene expression patterns from the Allen Brain Atlases can be seen here.

See also

References

  1. ↑ "Molecular cloning and chromosomal localization of the human alpha 7-nicotinic receptor subunit gene (CHRNA7)". Genomics 19 (2): 379–381. Jun 1994. doi:10.1006/geno.1994.1075. PMID 8188270. 
  2. ↑ "Entrez Gene: CHRNA7 cholinergic receptor, nicotinic, alpha 7". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1139. 
  3. ↑ "alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity". J. Biol. Chem. 276 (17): 13541–13546. April 2001. doi:10.1074/jbc.M008035200. PMID 11278378. 

Further reading

  • "Ion-channel assembly". Trends Neurosci. 18 (6): 280–287. 1995. doi:10.1016/0166-2236(95)93915-K. PMID 7571003. 
  • "Nicotinic acetylcholine receptors: from structure to brain function". Rev. Physiol. Biochem. Pharmacol.. Reviews of Physiology, Biochemistry and Pharmacology 147: 1–46. 2003. doi:10.1007/s10254-003-0005-1. ISBN 978-3-540-01365-5. PMID 12783266. 
  • "Immunologic role of the cholinergic anti-inflammatory pathway and the nicotinic acetylcholine alpha 7 receptor". Ann. N. Y. Acad. Sci. 1062: 209–219. 2005. doi:10.1196/annals.1358.024. PMID 16461803. 
  • "Human alpha 7 acetylcholine receptor: cloning of the alpha 7 subunit from the SH-SY5Y cell line and determination of pharmacological properties of native receptors and functional alpha 7 homomers expressed in Xenopus oocytes". Mol. Pharmacol. 45 (3): 546–554. 1994. PMID 8145738. 
  • "Generation and analysis of 280,000 human expressed sequence tags". Genome Res. 6 (9): 807–828. 1996. doi:10.1101/gr.6.9.807. PMID 8889549. 
  • "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): 217–228. 1996. doi:10.1007/BF02736842. PMID 8906617. 
  • "Pharmacological characterization of recombinant human neuronal nicotinic acetylcholine receptors h alpha 2 beta 2, h alpha 2 beta 4, h alpha 3 beta 2, h alpha 3 beta 4, h alpha 4 beta 2, h alpha 4 beta 4 and h alpha 7 expressed in Xenopus oocytes". J. Pharmacol. Exp. Ther. 280 (1): 346–356. 1997. PMID 8996215. 
  • "Cloning and sequence of full-length cDNAs encoding the human neuronal nicotinic acetylcholine receptor (nAChR) subunits beta3 and beta4 and expression of seven nAChR subunits in the human neuroblastoma cell line SH-SY5Y and/or IMR-32". FEBS Lett. 400 (3): 309–314. 1997. doi:10.1016/S0014-5793(96)01383-X. PMID 9009220. 
  • "Expression of the alpha 7 subunit of the nicotinic acetylcholine receptor in normal and myasthenic human thymuses". Cell. Mol. Biol. (Noisy-le-grand) 43 (3): 433–442. 1997. PMID 9193799. 
  • "Genomic organization and partial duplication of the human alpha7 neuronal nicotinic acetylcholine receptor gene (CHRNA7)". Genomics 52 (2): 173–185. 1998. doi:10.1006/geno.1998.5363. PMID 9782083. 
  • "No evidence for linkage between schizophrenia and markers at chromosome 15q13–14". Am. J. Med. Genet. 88 (2): 109–112. 1999. doi:10.1002/(SICI)1096-8628(19990416)88:2<109::AID-AJMG1>3.0.CO;2-3. PMID 10206225. 
  • "Evaluation of a putative major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q14". Am. J. Med. Genet. 88 (2): 182–187. 1999. doi:10.1002/(SICI)1096-8628(19990416)88:2<182::AID-AJMG16>3.0.CO;2-Z. PMID 10206240. 
  • "Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines". Neurosci. Lett. 266 (1): 17–20. 1999. doi:10.1016/S0304-3940(99)00259-1. PMID 10336173. 
  • "beta-Amyloid(1–42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology". J. Biol. Chem. 275 (8): 5626–5632. 2000. doi:10.1074/jbc.275.8.5626. PMID 10681545. 
  • "Interaction of tobacco-specific toxicants with the neuronal alpha(7) nicotinic acetylcholine receptor and its associated mitogenic signal transduction pathway: potential role in lung carcinogenesis and pediatric lung disorders". Eur. J. Pharmacol. 393 (1–3): 265–277. 2000. doi:10.1016/S0014-2999(00)00094-7. PMID 10771023. 
  • "alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity". J. Biol. Chem. 276 (17): 13541–13546. 2001. doi:10.1074/jbc.M008035200. PMID 11278378. 
  • "Linkage disequilibrium for schizophrenia at the chromosome 15q13–14 locus of the alpha7-nicotinic acetylcholine receptor subunit gene (CHRNA7)". Am. J. Med. Genet. 105 (1): 20–22. 2001. doi:10.1002/1096-8628(20010108)105:1<20::AID-AJMG1047>3.0.CO;2-C. PMID 11424985. 
  • "Changes in nicotinic acetylcholine receptor subunits expression in brain of patients with Down syndrome and Alzheimer's disease". Protein Expression in Down Syndrome Brain. Journal of Neural Transmission. Supplementum. 2001. pp. 211–222. doi:10.1007/978-3-7091-6262-0_17. ISBN 978-3-211-83704-7. 

External links

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



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