High impact information on nAcRalpha-96Ab

• Comparison of the yeast alpha 2 and the Drosophila engrailed homeodomain-DNA complexes shows that the protein fold is highly conserved, despite a 3-residue insertion in alpha 2 and only 27% sequence identity between the two homeodomains [1].
• We have determined the 2.7 A resolution crystal structure of the alpha 2 homeodomain bound to a biologically relevant DNA sequence [1].
• This region of alpha 2 has significant homology with the homeo domain, a conserved sequence found in the products of several Drosophila homeotic and segmentation genes [2].
• The Drosophila tyramine receptor that we have isolated might therefore be an invertebrate equivalent of the mammalian alpha 2 adrenergic receptors [3].
• Membranes from mammalian cells expressing this receptor displayed high affinity binding sites for [3H]yohimbine, an alpha 2 adrenergic receptor antagonist (Kd = 4.45 x 10(-9) M) [3].

Biological context of nAcRalpha-96Ab

• Five different D alpha 2-lacZ fusion gene constructs were introduced into the Drosophila genome by P-element-mediated gene transfer to identity functional elements of the D alpha 2 promoter [4].
• Between 1.7 and 7.3 kb upstream of the transcription start site one or more elements that are required for D alpha 2 expression in optic lobe tangential cells are located [4].
• Cytogenetically, the D alpha 2 gene maps at position 96A of the 3rd chromosome, close to the ALS gene which also encodes an alpha-like nAChR subunit [5].
• On considering both neonicotinoids and nicotinoids, the Dalpha2/Rbeta2 and Mpalpha2/Rbeta2 receptors display intermediate pharmacological profiles between those of native insect and vertebrate alpha4beta2 receptors, limiting the use of these hybrid receptors for predictive toxicology [6].
• Identity between the nucleotide sequences of alpha 1 and alpha 2 was 83.4%; between their predicted amino acid sequences it was 88.9% [7].

Anatomical context of nAcRalpha-96Ab

• Transcripts and protein from the D alpha 2 gene were detected exclusively in the central nervous system [4].
• Both in late embryos and adults D alpha 2-like immunoreactivity is widely but not uniformly distributed in the synaptic neuropil, suggesting that the D alpha 2 protein is a subunit of a synaptic nicotinic receptor [4].
• 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 [8].
• Our results suggest that both the alpha1 and alpha2 collagen IV chains may contribute to basement membranes in Drosophila [9].
• Transformation of chick embryo fibroblasts (CEFs) by the v-Jun oncoprotein correlates with a downregulation of the alpha 2 (I) collagen gene [10].

Associations of nAcRalpha-96Ab with chemical compounds

• This is the first demonstration that imidacloprid selectively acts on Mp alpha2 and Mp alpha3 subunits, but not Mp alpha1, in M. persicae [11].
• Expression of the ligand-binding nicotinic acetylcholine receptor subunit D alpha 2 in the Drosophila central nervous system [4].
• 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 [12].
• Two-dimensional gel electrophoresis separated at least 28 proteins, 13 of which were identified with monospecific antibodies to alpha6/C2 (five species), alpha2/C3 (three species), alpha7/C8 (three species), alpha5/zeta, and beta1/Y subunits [13].

Regulatory relationships of nAcRalpha-96Ab

• A chimera based on the chicken alpha4 nicotinic acetylcholine receptor (nAChR) subunit containing an insert from loop B to the N-terminus of the Drosophila melanogaster Dalpha2 (=SAD) subunit was constructed and co-expressed with the chicken beta2 nAChR subunit in Xenopus laevis oocytes [14].

Other interactions of nAcRalpha-96Ab

• Sequencing of the alpha 3EpA transcript indicated sequence and structural homology to laminin alpha 1 and alpha 2 chains that extend from domain IIIa through the carboxyl-terminal G domain [15].
• Two of the five chimeric subunits, Cfalpha1/Dalpha2 and Cfalpha3/Dalpha2, when co-expressed with rat beta2 in Drosophila S2 cells, showed high-affinity binding of both epibatidine (Kd=1.6+/-0.6 and 0.13+/-0.06nM, respectively), and imidacloprid (Ki=142+/-34 and 28.7+/-2.4nM, respectively) [16].
• Replacement of the region loop B to the N-terminus of the alpha4 subunit by the corresponding region of the Dalpha2 subunit had little effect on the concentration-response curve for imidacloprid [14].
• The temporal and spatial expression pattern of the Drosophila melanogaster alpha 2-tubulin gene (alpha 2) has been investigated by examining the expression of an alpha 2-lacZ fusion gene [17].
• v-Jun downregulates the alpha 2 (I) collagen target gene indirectly through Sp1/3 [10].

Analytical, diagnostic and therapeutic context of nAcRalpha-96Ab

• Gel filtration indicated the formation of an alpha 2 beta 2 tetramer [18].

References