CHRNA7 explained

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

• Alpha-7 nicotinic receptor
• Nicotinic acetylcholine receptor
• Acetylcholine receptor

Further reading

• Green WN, Millar NS . Ion-channel assembly . Trends Neurosci. . 18 . 6 . 280–287 . 1995 . 7571003 . 10.1016/0166-2236(95)93915-K .
• Hogg RC, Raggenbass M, Bertrand D . Nicotinic acetylcholine receptors: from structure to brain function . Rev. Physiol. Biochem. Pharmacol. . Reviews of Physiology, Biochemistry and Pharmacology . 147 . 1–46 . 2003 . 12783266 . 10.1007/s10254-003-0005-1 . 978-3-540-01365-5 .
• Gallowitsch-Puerta M, Tracey KJ . Immunologic role of the cholinergic anti-inflammatory pathway and the nicotinic acetylcholine alpha 7 receptor . Ann. N. Y. Acad. Sci. . 1062 . 209–219 . 2005 . 1 . 16461803 . 10.1196/annals.1358.024 . 2005NYASA1062..209G . 22980405 .
• Peng X, Katz M, Gerzanich V, Anand R, Lindstrom J . 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 . 8145738 .
• Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, Dietrich N, DuBuque T, Favello A, Gish W, Hawkins M, Hultman M, Kucaba T, Lacy M, Le M, Le N, Mardis E, Moore B, Morris M, Parsons J, Prange C, Rifkin L, Rohlfing T, Schellenberg K, Bento Soares M, Tan F, Thierry-Meg J, Trevaskis E, Underwood K, Wohldman P, Waterston R, Wilson R, Marra M . Generation and analysis of 280,000 human expressed sequence tags . Genome Res. . 6 . 9 . 807–828 . 1996 . 8889549 . 10.1101/gr.6.9.807 . free .
• Elliott KJ, Ellis SB, Berckhan KJ, Urrutia A, Chavez-Noriega LE, Johnson EC, Veliçelebi G, Harpold MM . 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 . 8906617 . 10.1007/BF02736842 . 45737923 .
• Chavez-Noriega LE, Crona JH, Washburn MS, Urrutia A, Elliott KJ, Johnson EC . 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 . 8996215 .
• Groot Kormelink PJ, Luyten WH . 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 . 9009220 . 10.1016/S0014-5793(96)01383-X . free .
• Navaneetham D, Penn A, Howard J, Conti-Fine BM . 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 . 9193799 .
• Gault J, Robinson M, Berger R, Drebing C, Logel J, Hopkins J, Moore T, Jacobs S, Meriwether J, Choi MJ, Kim EJ, Walton K, Buiting K, Davis A, Breese C, Freedman R, Leonard S . Genomic organization and partial duplication of the human alpha7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) . Genomics . 52 . 2 . 173–185 . 1998 . 9782083 . 10.1006/geno.1998.5363 .
• Curtis L, Blouin JL, Radhakrishna U, Gehrig C, Lasseter VK, Wolyniec P, Nestadt G, Dombroski B, Kazazian HH, Pulver AE, Housman D, Bertrand D, Antonarakis SE . No evidence for linkage between schizophrenia and markers at chromosome 15q13–14 . Am. J. Med. Genet. . 88 . 2 . 109–112 . 1999 . 10206225 . 10.1002/(SICI)1096-8628(19990416)88:2<109::AID-AJMG1>3.0.CO;2-3 .
• Sander T, Schulz H, Vieira-Saeker AM, Bianchi A, Sailer U, Bauer G, Scaramelli A, Wienker TF, Saar K, Reis A, Janz D, Epplen JT, Riess O . Evaluation of a putative major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q14 . Am. J. Med. Genet. . 88 . 2 . 182–187 . 1999 . 10206240 . 10.1002/(SICI)1096-8628(19990416)88:2<182::AID-AJMG16>3.0.CO;2-Z .
• Sato KZ, Fujii T, Watanabe Y, Yamada S, Ando T, Kazuko F, Kawashima K . 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 . 10336173 . 10.1016/S0304-3940(99)00259-1 . 43548155 .
• Wang HY, Lee DH, D'Andrea MR, Peterson PA, Shank RP, Reitz AB . 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 . 10681545 . 10.1074/jbc.275.8.5626 . free .
• Schuller HM, Jull BA, Sheppard BJ, Plummer HK . 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 . 10771023 . 10.1016/S0014-2999(00)00094-7 .
• Kihara T, Shimohama S, Sawada H, Honda K, Nakamizo T, Shibasaki H, Kume T, Akaike A . 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 . 11278378 . 10.1074/jbc.M008035200 . free .
• Freedman R, Leonard S, Gault JM, Hopkins J, Cloninger CR, Kaufmann CA, Tsuang MT, Farone SV, Malaspina D, Svrakic DM, Sanders A, Gejman P . 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 . 11424985 . 10.1002/1096-8628(20010108)105:1<20::AID-AJMG1047>3.0.CO;2-C . 37412240 .
• Book: Engidawork E, Gulesserian T, Balic N, Cairns N, Lubec G . 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 . Lubec G. 61 . 211–222 . 2001 . 11771745 . 10.1007/978-3-7091-6262-0_17 . 978-3-211-83704-7 .

Notes and References

1. Chini B, Raimond E, Elgoyhen AB, Moralli D, Balzaretti M, Heinemann S . Molecular cloning and chromosomal localization of the human alpha 7-nicotinic receptor subunit gene (CHRNA7) . Genomics . 19 . 2 . 379–381 . Jun 1994 . 8188270 . 10.1006/geno.1994.1075 .
2. Web site: Entrez Gene: CHRNA7 cholinergic receptor, nicotinic, alpha 7.
3. Kihara T, Shimohama S, Sawada H, Honda K, Nakamizo T, Shibasaki H, Kume T, Akaike A . 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 . 11278378 . 10.1074/jbc.M008035200 . free .