nicotinic receptor alpha-7, neuronal acetylcholine receptor subunit alpha-7 (CHRNA7, NACHRA7, alpha 7 nAChR)
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Function
- nicotinic receptor alpha subunit
- selectively bound by alpha-bungarotoxin.[5] the channel is blocked by alpha-bungarotoxin
- interaction with RIC3 is required for proper folding & assembly
- forms functional homopentamers, ligand-gated ion channels linked to rapidly desensitizing Ca2+ influx.[4]
- diminishes phagocyte (microglia, macrophage) inflammatory response on binding of acetylcholine or nicotine
- role in modulation of release of several neurotransmitters, mediating &/or modulating synaptic transmission, plasticity, & neurodegeneration (putative)[5]
- postsynaptically, CHRNA7 may undergo dynamic regulation, with insertion into the synapse & subsequent internalization[5]
- stimulation of CHRNA7 transduces signals to phosphatidylinositol 3-kinase & Akt, via Janus kinase 2 (JAK2)
Structure
- homopentamer
- belongs to the ligand-gated ionic channel (TC 1.A.9) family
- mass spec: mass=54157.68; method=MALDI; Range=23-502[8]
Compartment
- cell junction, synapse, postsynaptic cell membrane
- present in both presynaptic & postsynaptic membranes
Alternative splicing
named isoforms=3
Expression
- present on macrophages in the periphery & microglia in the CNS
- widely expressed throughout the mammalian brain[4]
- present at nearly all synapses in CA1 stratum radiatum
- GABAergic & glutamatergic synapses bear alpha7 nAChRs, at densities approaching those observed for glutamate receptors in CA1 stratum radiatum
Pathology
- stimulation of CHRNA7 may result in neuroprotection from the toxicity of the amyloid beta-peptide via signals from phosphatidylinositol 3-kinase & Akt, via Janus kinase 2 (JAK2)[4]
Comparative biology
- a segmental duplication of chromosome 15 involving CHRNA7 & Fam7A is one of the few features distinguishing the human genome from the chimpanzee genome[6][7]
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/P36544.html
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1139
- ↑ Chemical & Engineering News, March 27, 2004 pg 8 Wang H et al Nature 421:384, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12508119 J Tan & RD Shytle, J Neurochem (Mar 8) http://www.blackwell-synergy.com/links/doi/10.1046/j.1471-4159.2004.02347.x
- ↑ 4.0 4.1 4.2 4.3 Shaw S, Bencherif M, Marrero MB. Janus kinase 2, an early target of alpha 7 nicotinic acetylcholine receptor-mediated neuroprotection against Abeta-(1-42) amyloid. J Biol Chem. 2002 Nov 22;277(47):44920-4. Epub 2002 Sep 18. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12244045
- ↑ 5.0 5.1 5.2 5.3 Fabian-Fine R, Skehel P, Errington ML, Davies HA, Sher E, Stewart MG, Fine A. Ultrastructural distribution of the alpha7 nicotinic acetylcholine receptor subunit in rat hippocampus. J Neurosci. 2001 Oct 15;21(20):7993-8003. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11588172
- ↑ 6.0 6.1 Riley B, Williamson M, Collier D, Wilkie H, Makoff A. A 3-Mb map of a large Segmental duplication overlapping the alpha7-nicotinic acetylcholine receptor gene (CHRNA7) at human 15q13-q14. Genomics. 2002 Feb;79(2):197-209. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11829490
- ↑ 7.0 7.1 Fortna A, Kim Y, MacLaren E, Marshall K, Hahn G, Meltesen L, Brenton M, Hink R, Burgers S, Hernandez-Boussard T, Karimpour- Fard A, Glueck D, McGavran L, Berry R, Pollack J, Sikela JM. Lineage-specific gene duplication and loss in human and great ape evolution. PLoS Biol. 2004 Jul;2(7):E207. Epub 2004 Jul 13. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15252450
- ↑ 8.0 8.1 Mass spec data PMID: https://www.ncbi.nlm.nih.gov/pubmed/11840567
- ↑ PMID: https://www.ncbi.nlm.nih.gov/pubmed/16120769
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1139
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=89832
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1139
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:89832
- OMIM: https://mirror.omim.org/entry/118511
- UniProt: http://www.uniprot.org/uniprot/P36544.html