High impact information on nAcRalpha-30D

• The analysis showed that the first 4 exons and the last exon of all muscle and brain nAChR subunit genes have the same boundaries, with the exception of a nAChR-related gene in Drosophila [1].
• There is a large group of divergent C. elegans nAChR-like subunits partially resolved into clades but no orthologues of 5HT3-type serotonin receptors in the invertebrates [2].
• In the present study, we report the first isolation of a full-length Dalpha7 cDNA and the independent molecular cloning of Dalpha6 [3].
• The coplanar system between the electronegative tip and guanidine-amidine moiety extends the conjugation and facilitates negative charge (delta(-)) flow toward the tip, thereby enhancing interaction with the proposed cationic subsite such as lysine or arginine in the Drosophila nAChR [4].
• The Dalpha6 transcript is a target of the Drosophila adenosine deaminase acting on RNA (dADAR) [5].

Biological context of nAcRalpha-30D

• Alternative splicing in Dalpha6 involves exons encoding nAChR functional domains [5].
• Embryonic clones from Dalpha6 contain multiple variant transcripts arising from alternative splicing as well as A-to-I pre-mRNA editing [5].
• Molecular characterization of Dalpha6 and Dalpha7 nicotinic acetylcholine receptor subunits from Drosophila: formation of a high-affinity alpha-bungarotoxin binding site revealed by expression of subunit chimeras [3].
• Indeed, RNA-editing sites identified in functionally significant regions of Dbeta1, Dalpha5, and Dalpha6 are not conserved in the mosquito orthologues, indicating considerable divergence of RNA molecules targeted for editing within the insect order Diptera [6].
• We have identified the nAChR gene family from the genome of the malaria mosquito vector, Anopheles gambiae, to be the second complete insect nAChR gene family described following that of Drosophila melanogaster [6].

Anatomical context of nAcRalpha-30D

• This compound (unlabeled) has an IC50 of 8 nM for [3H]-IMI binding in Drosophila head membranes, and the 125I-labeled photoaffinity probe labels only a 66 kDa protein(s) at a specific site inhibited by (-)-nicotine, consistent with the insecticide-binding subunit of the nAChR [7].
• The vertebrate nAChR, assembled from five homologous subunits, penetrates the synaptic membrane [8].

Associations of nAcRalpha-30D with chemical compounds

• Seven adenosines could be modified in the extracellular ligand-binding region of Dalpha6, four of which are also edited in the Dalpha6 ortholog in the tobacco budworm Heliothis virescens [5].
• We propose that neonicotinoids with a protonated N-unsubstituted imine or equivalent substituent recognize the anionic subsite of the mammalian alpha4beta2 nAChR whereas the negatively charged (delta(-)) tip of the neonicotinoid insecticides interacts with a putative cationic subsite of the insect nAChR [9].
• The insect nicotinic acetylcholine receptor (nAChR) is the target for the major insecticide imidacloprid (IMI) and for the first candidate photoaffinity probe described here [7].
• With the Drosophila nAChR assay, the N-methyl compounds N-methyl-imidacloprid and thiamethoxam are activated 4.5-29-fold by CYP3 A4 whereas nine other neo-nicotinoids are not changed in potency [10].
• This study clearly showed that nitroimines, nitromethylenes, and cyanoimines are more selective to Drosophila nAChR and safe for human being, whereas N-substituted imines have affinity to mammalian receptor [11].

Other interactions of nAcRalpha-30D

• As with Dalpha4 and Dalpha6, the Anopheles orthologues are alternatively spliced at equivalent exons [6].

Analytical, diagnostic and therapeutic context of nAcRalpha-30D

• The genes coding for the beta and epsilon subunits of the mouse muscle nicotinic acetylcholine receptor (nAChR) were mapped by Southern blot analysis, and the entire loci for both genes cloned [1].
• Sequence analysis has identified an open reading frame of 509 amino acids with features typical of nAChR subunits [12].
• The insect nAChR is the primary target site for the neonicotinoid insecticides, thereby providing an incentive to explore its functional architecture with neonicotinoid radioligands, photoaffinity probes and affinity chromatography matrices [8].
• This new preparation, in which whole-cell recordings and pharmacology can be combined with genetic approaches, will be critical in understanding the contribution of nAChR-mediated fast synaptic transmission to cellular plasticity in the neural circuits underlying olfactory associative learning [13].

References