Disease relevance of Ace

• High levels of expression of the Aedes gene were achieved by infection of Sf21 cells with a recombinant baculovirus containing the Aedes Ace cDNA [1].
• Selective cleavage by Staphylococcus aureus phosphatidylinositol-specific phospholipase C (PI-PLC) was tested with Drosophila AChE radiolabeled by the photoactivatable affinity probe 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine [( 125I]TID), a reagent that specifically labels the lipid moiety of glycoinositol phospholipid-anchored proteins [2].
• Cloning, sequencing and functional expression of an acetylcholinesterase gene from the yellow fever mosquito Aedes aegypti [1].
• An amino acid substitution attributable to insecticide-insensitivity of acetylcholinesterase in a Japanese encephalitis vector mosquito, Culex tritaeniorhynchus [3].
• Do metals inhibit acetylcholinesterase (AChE)? Implementation of assay conditions for the use of AChE activity as a biomarker of metal toxicity [4].

Psychiatry related information on Ace

• Rivastigmine, a carbamate inhibitor of acetylcholinesterase, is already in use for treatment of Alzheimer's disease under the trade name of Exelon [5].
• In order to study critical periods for the effects of mutant AChE, temperature-sensitive mutations of the Ace gene were isolated [6].

High impact information on Ace

• In ecdysone-sensitive Drosophila Kc cells, the insecticide RH 5849 (1,2-dibenzoyl-1-tert-butylhydrazine) mimics the action of 20-hydroxyecdysone by causing the formation of processes, an inhibition of cell proliferation, and induction of acetylcholinesterase [7].
• When cells of the Drosophila Kc-H line are treated with larger than or equal to 10(-8) molar beta-ecdysone, they extend long processes and acquire acetylcholinesterase activity [8].
• Induction of acetylcholinesterase activity by beta-ecdysone in a Drosophila cell line [8].
• As we found previously for a gene whose product is also involved in cholinergic synapses, acetylcholinesterase, the leader encodes short open reading frames, which might be involved in translation control [9].
• cDNA sequences of Torpedo marmorata acetylcholinesterase: primary structure of the precursor of a catalytic subunit; existence of multiple 5'-untranslated regions [10].

Biological context of Ace

• Kinesin-2 differentially regulates the anterograde axonal transports of acetylcholinesterase and choline acetyltransferase in Drosophila [11].
• The normal in vitro expression pattern for ChAT and AChE can be altered by adding various cholinergic drugs to the culture medium during cell differentiation [12].
• We have compared the amino acid sequences of proteins that are involved in acetylcholine (AcCho) metabolism and cholinergic neurotransmission: choline acetyltransferase (ChoAcTase), acetylcholinesterase (AcChoEase), and a neuronal alpha subunit of nicotinic AcCho receptor (AcChoR) [13].
• In contrast, none of these post-translational modifications significantly affects the activity of acetylcholinesterase or affinity for its substrate [14].
• Post-translational modifications of Drosophila acetylcholinesterase. In vitro mutagenesis and expression in Xenopus oocytes [14].

Anatomical context of Ace

• The projections of adult peripheral neurons innervating Ace+ tissue from Ace cuticular clones has been examined to address the nature of the structure of Ace neuropil [15].
• Active Drosophila acetylcholinesterase can be expressed in Xenopus oocytes as an excreted protein [14].
• Drosophila acetylcholinesterase (EC 3.1.1.7) is a 150-kDa glycoprotein anchored in plasmic membranes via a glycolipid [14].
• Mosaics with Ace mutant tissue in the first-order optic lobe, the lamina, lacked a synaptic component of the electroretinogram, the "off" transient [6].
• The transcript of the acetylcholinesterase gene (Ace) was detected in the central nervous system (CNS) and the lateral chordotonal neurons (lch3, lch5) of wild type Drosophila melanogaster embryos [16].

Associations of Ace with chemical compounds

• Exploration of the Drosophila acetylcholinesterase substrate activation site using a reversible inhibitor (Triton X-100) and mutated enzymes [17].
• Drosophila acetylcholinesterase exhibits four effective sites of asparagine-linked glycosylation in positions 126, 174, 331, and 531 [14].
• Homotropic cooperativity in Drosophila melanogaster acetylcholinesterase seems to be a consequence of an initial substrate binding to a high-affinity peripheral substrate binding site situated around the negative charge of D413 (G335, Torpedo numbering) [18].
• Insect acetylcholinesterase is the target site for organophosphorus and carbamate insecticides and point mutations in the Ace gene are associated with resistance in Drosophila melanogaster and Musca domestica [19].
• This DNA fragment, designated Huache 1R, bears sequence homology to a DNA fragment from the vicinity of the Drosophila Ace region, that controls AChE biosynthesis (Soreq et al., 1985) [20].

Physical interactions of Ace

• AChE transport is constitutive while that of ChAT occurs in a brief pulse during third instar larva stage [11].

Other interactions of Ace

• The results obtained in these studies are discussed with respect to data presented on the adult distribution of the cholinergic markers' AChE activity and ChAT immunoreactivity [15].
• Interestingly, despite the complexity of the encoded receptors or enzymes, very few amino acid residues are replaced in different resistant insects: one within RDL, two within PARA and three or more within AChE [21].
• The walk includes the DNA for the rosy and Ace loci, which code for xanthine dehydrogenase and acetylcholinesterase, respectively [22].
• Chromosomal walking and jumping to isolate DNA from the Ace and rosy loci and the bithorax complex in Drosophila melanogaster [22].
• The cells in these cultures had the properties of neurons of the Drosophila CNS: They gave rise to ganglion-like clusters from which neurites extended on the culture substrate, and they expressed the enzyme, acetylcholinesterase, and the cell surface antigens recognized by antisera raised against horseradish peroxidase [23].

Analytical, diagnostic and therapeutic context of Ace

• Western blots with two antibodies directed against the N- and C-termini of the predicted AChE primary sequence show that the 55 and 16 kDa polypeptides originate from proteolysis of the same precursor encoded by the Ace locus [24].
• To detect traces of insecticides in the environment using biosensors, we engineered Drosophila acetylcholinesterase (AChE) to increase its sensitivity and its rate of phosphorylation or carbamoylation by organophosphates or carbamates [25].
• Here, we report the sequence analysis of the Ace gene in several resistant field strains of Drosophila melanogaster [26].
• We have focused on Drosophila acetylcholinesterase (AChE) as a model GPI-anchored protein that can be manipulated in vivo with sophisticated genetic techniques [27].
• However, light level and electron microscopic immunocytochemistry showed no differences in the localization of GPI- and TM-AChE [28].

References