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Gene Review

nAChRalpha1  -  nicotinic Acetylcholine Receptor alpha1

Drosophila melanogaster

Synonyms: ALS, ALs, Acetylcholine receptor subunit alpha-like 1, Acr96A, Acr96Aa, ...
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High impact information on nAcRalpha-96Aa

  • We demonstrate that alpha1, 2 laminin and alphaPS3betaPS integrin are required for the spreading of a small group of cells of the amnioserosa epithelium over the tail end of the germ band [1].
  • By systematic expression screening of novel putative ligand-gated anion channels, we identified two cDNAs (DM-HisCl-alpha 1 and-alpha 2) coding for putative histamine-gated chloride channels by functional expression in Xenopus laevis oocytes [2].
  • The deduced amino acid sequence displays high homology to the ALS protein and shares structural features with ligand binding nAChR alpha-subunits [3].
  • Nicotinic acetylcholine receptors (nAChR) are found both in vertebrate and insect central nervous systems [4].
  • Neonicotinoids, such as imidacloprid, are nicotinic acetylcholine receptor (nAChR) agonists with potent insecticidal activity [5].

Biological context of nAcRalpha-96Aa


Anatomical context of nAcRalpha-96Aa

  • Immunohistochemical studies in the adult optic lobe revealed that SBD has a distribution similar to that of the alpha-subunit ALS in the synaptic neuropil [11].
  • In embryos, sbd and als transcripts are localized in the central nervous system [12].
  • Immunoprecipitation experiments of fly head extracts revealed that ALS-specific antibodies coprecipitate Dalpha2, and vice versa, and thereby suggest that these two alpha subunits must be contained within the same receptor complex, a result that is supported by investigations of reconstituted receptors in Xenopus oocytes [13].
  • Immunohistochemical evidence has suggested that two alpha subunits, alpha-like subunit (ALS) and Drosophila alpha2 subunit (Dalpha2), are colocalized in the synaptic neuropil of the Drosophila CNS and therefore may be subunits of the same receptor complex [13].
  • Both ALS and ARD antisera removed 20-30% of the high-affinity binding sites for the nicotinic antagonist 125I-alpha-bungarotoxin (125I-alpha-Btx) from detergent extracts of fly head membranes [14].

Associations of nAcRalpha-96Aa with chemical compounds

  • The efficiency of subunit assembly has been shown to be influenced by amino acids surrounding the highly conserved 15 amino acid cysteine-loop motif within the N-terminal extracellular domain of the nAChR Dalpha4 subunit [6].
  • Because the alpha1 isoform is sensitive to cardiac glycosides in humans, we developed mice in which the naturally occurring ouabain-resistant alpha1 isoform was made ouabain-sensitive [15].
  • These results demonstrate that the Drosophila ALS and D alpha 2 cDNAs encode neuronal nicotinic subunits responding to physiological concentrations of the agonists acetylcholine and nicotine [16].
  • However, replacement of Glu219 by proline in the YXCC motif in loop C of the chimeric alpha4 subunit resulted in a marked displacement to the left of the concentration-response curve for imidacloprid not seen when an equivalent mutation was made in the alpha4beta2 nAChR [17].
  • The alpha1, 2-mannosidase loses its activity in the presence of dithiothreitol with first order kinetics, suggesting that at least one disulfide bond is essential for activity [18].

Other interactions of nAcRalpha-96Aa

  • In addition, SBD appears to be a component of a different receptor complex, which includes the ARD protein as an additional beta-subunit, but neither ALS nor D(alpha)2 nor the third alpha-subunit D(alpha)3 [11].
  • The subunits ALS, D(alpha)2 and SBD can be co-purified by alpha-bungarotoxin affinity chromatography [11].
  • However, unlike D. melanogaster, in all montium species studied, both alpha 1- and alpha 3-tubulin specific probes hybridize to the same polytene band, indicating a clustered organization of the above genes [19].
  • The D. melanogaster Pp1-96A-Acr96Aa segment conserved in D. repleta and D. buzzatii is longer than previously thought and is also conserved in D. virilis [20].
  • Strikingly, the rat alpha1 isoform has full junctional activity and can rescue Atpalpha-null mutants to viability, suggesting that the Na,K-ATPase has an evolutionarily conserved role in junction formation and function [21].

Analytical, diagnostic and therapeutic context of nAcRalpha-96Aa

  • Verification using real-time PCR shows that pan-neuronal expression of eve is sufficient to repress transcripts for both slo and nAcRalpha-96Aa [7].
  • Detergent-solubilized receptor complexes containing the cross-linked products were immunoprecipitated by antisera against two nAChR subunits previously identified by molecular cloning, the ALS and ARD proteins, suggesting that the 42 kDa toxin binding polypeptide constitutes a component of the previously described class 1 alpha-Btx binding site [22].
  • The DGC alpha 1 protein was also localized primarily to the nervous system by immunocytochemical staining, consistent with results of in situ hybridization [23].
  • Immunohistochemistry with anti-SIX4/AREC3 and anti-Na, K-ATPase alpha 1 subunit antisera was performed on developing mouse retinas, and immunoblotting analysis with anti-SIX4/AREC3 was also performed [24].


  1. Retraction of the Drosophila germ band requires cell-matrix interaction. Schöck, F., Perrimon, N. Genes Dev. (2003) [Pubmed]
  2. Two cDNAs coding for histamine-gated ion channels in D. melanogaster. Gisselmann, G., Pusch, H., Hovemann, B.T., Hatt, H. Nat. Neurosci. (2002) [Pubmed]
  3. Heterogeneity of Drosophila nicotinic acetylcholine receptors: SAD, a novel developmentally regulated alpha-subunit. Sawruk, E., Schloss, P., Betz, H., Schmitt, B. EMBO J. (1990) [Pubmed]
  4. Conservation of neural nicotinic acetylcholine receptors from Drosophila to vertebrate central nervous systems. Bossy, B., Ballivet, M., Spierer, P. EMBO J. (1988) [Pubmed]
  5. A nicotinic acetylcholine receptor mutation conferring target-site resistance to imidacloprid in Nilaparvata lugens (brown planthopper). Liu, Z., Williamson, M.S., Lansdell, S.J., Denholm, I., Han, Z., Millar, N.S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. Cloning and heterologous expression of Dalpha4, a Drosophila neuronal nicotinic acetylcholine receptor subunit: identification of an alternative exon influencing the efficiency of subunit assembly. Lansdell, S.J., Millar, N.S. Neuropharmacology (2000) [Pubmed]
  7. The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons. Pym, E.C., Southall, T.D., Mee, C.J., Brand, A.H., Baines, R.A. Neural development (2006) [Pubmed]
  8. Crystal structure of an enhancer of rudimentary homolog (ERH) at 2.1 Angstroms resolution. Arai, R., Kukimoto-Niino, M., Uda-Tochio, H., Morita, S., Uchikubo-Kamo, T., Akasaka, R., Etou, Y., Hayashizaki, Y., Kigawa, T., Terada, T., Shirouzu, M., Yokoyama, S. Protein Sci. (2005) [Pubmed]
  9. Structure and developmental expression of the D alpha 2 gene encoding a novel nicotinic acetylcholine receptor protein of Drosophila melanogaster. Jonas, P., Baumann, A., Merz, B., Gundelfinger, E.D. FEBS Lett. (1990) [Pubmed]
  10. Molecular characterization of four members of the alpha-tubulin gene family of the Bermuda land crab Gecarcinus lateralis. Varadaraj, K., Kumari, S.S., Skinner, D.M. J. Exp. Zool. (1997) [Pubmed]
  11. Nicotinic acetylcholine receptors of Drosophila: three subunits encoded by genomically linked genes can co-assemble into the same receptor complex. Chamaon, K., Smalla, K.H., Thomas, U., Gundelfinger, E.D. J. Neurochem. (2002) [Pubmed]
  12. SBD, a novel structural subunit of the Drosophila nicotinic acetylcholine receptor, shares its genomic localization with two alpha-subunits. Sawruk, E., Udri, C., Betz, H., Schmitt, B. FEBS Lett. (1990) [Pubmed]
  13. Neuronal nicotinic acetylcholine receptors from Drosophila: two different types of alpha subunits coassemble within the same receptor complex. Schulz, R., Bertrand, S., Chamaon, K., Smalla, K.H., Gundelfinger, E.D., Bertrand, D. J. Neurochem. (2000) [Pubmed]
  14. Neuronal nicotinic acetylcholine receptors in Drosophila: antibodies against an alpha-like and a non-alpha-subunit recognize the same high-affinity alpha-bungarotoxin binding complex. Schloss, P., Betz, H., Schröder, C., Gundelfinger, E.D. J. Neurochem. (1991) [Pubmed]
  15. The highly conserved cardiac glycoside binding site of Na,K-ATPase plays a role in blood pressure regulation. Dostanic-Larson, I., Van Huysse, J.W., Lorenz, J.N., Lingrel, J.B. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  16. Physiological properties of neuronal nicotinic receptors reconstituted from the vertebrate beta 2 subunit and Drosophila alpha subunits. Bertrand, D., Ballivet, M., Gomez, M., Bertrand, S., Phannavong, B., Gundelfinger, E.D. Eur. J. Neurosci. (1994) [Pubmed]
  17. Insect-vertebrate chimeric nicotinic acetylcholine receptors identify a region, loop B to the N-terminus of the Drosophila Dalpha2 subunit, which contributes to neonicotinoid sensitivity. Shimomura, M., Satoh, H., Yokota, M., Ihara, M., Matsuda, K., Sattelle, D.B. Neurosci. Lett. (2005) [Pubmed]
  18. Role of the cysteine residues in the alpha1,2-mannosidase involved in N-glycan biosynthesis in Saccharomyces cerevisiae. The conserved Cys340 and Cys385 residues form an essential disulfide bond. Lipari, F., Herscovics, A. J. Biol. Chem. (1996) [Pubmed]
  19. The organization of the alpha-tubulin gene family in the Drosophila montium subgroup of the melanogaster species group. Drosopoulou, E., Scouras, Z.G. Genome (1998) [Pubmed]
  20. Comparative mapping of cosmids and gene clones from a 1.6 Mb chromosomal region of Drosophila melanogaster in three species of the distantly related subgenus Drosophila. Ranz, J.M., Cáceres, M., Ruiz, A. Chromosoma (1999) [Pubmed]
  21. A pump-independent function of the Na,K-ATPase is required for epithelial junction function and tracheal tube-size control. Paul, S.M., Palladino, M.J., Beitel, G.J. Development (2007) [Pubmed]
  22. Cross-linking of 125I-alpha-bungarotoxin to Drosophila head membranes identifies a 42 kDa toxin binding polypeptide. Schloss, P., Mayser, W., Gundelfinger, E.D., Betz, H. Neurosci. Lett. (1992) [Pubmed]
  23. Molecular characterization of two Drosophila guanylate cyclases expressed in the nervous system. Liu, W., Yoon, J., Burg, M., Chen, L., Pak, W.L. J. Biol. Chem. (1995) [Pubmed]
  24. Localization of Six4/AREC3 in the developing mouse retina; implications in mammalian retinal development. Niiya, A., Ohto, H., Kawakami, K., Araki, M. Exp. Eye Res. (1998) [Pubmed]
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