Disease relevance of ace-1

• Spodoptera Sf9 cells were infected by a recombinant baculovirus containing ace-1 cDNA [1].

High impact information on ace-1

• The single ace-1+ gene in these animals is responsible for coordinated animal movement and acetylcholinesterase activity in the regions of the nerve ring and ventral and dorsal nerve cords, as judged by histochemical assay [2].
• We have generated C. elegans animals that carry a duplication as a free chromosome fragment bearing an ace-1+ gene in an otherwise homozygous ace-1 ace-2 genetic background [2].
• In contrast, ace-1 ace-2 ace-3 triple mutant animals are paralyzed and developmentally arrested; their embryonic development is relatively unimpaired, but they are unable to grow beyond the hatching stage [3].
• Acetylcholine activity is terminated by hydrolysis by acetylcholinesterase (AChE) [4].
• It encodes an H subunit that associates into dimers of glycolipid-anchored catalytic subunits, which are highly resistant to the usual AChE inhibitors, and which hydrolyze butyrylthiocholine faster than acetylthiocholine [5].

Biological context of ace-1

• This fragment mapped to chromosome X at a position that perfectly matched the location of ace-1 previously determined by genetic methods [1].
• Clear homologues of ace-1 and ace-2 have now been isolated from a variety of parasitic nematodes, and the predicted proteins have very similar C-terminal amino acid sequences, implying an analogous means of anchorage to membranes [6].
• The gene ace-1 has been mapped near the right end of the X chromosome [7].
• ace-1 and ace-2 genes encoding acetylcholinesterase in the nematode Caenorhabditis elegans present 35% identity in coding sequences but no homology in noncoding regions (introns, 5'- and 3'-untranslated regions) [8].
• When green fluorescent protein (GFP) expression was driven by this regulatory region, the resulting pattern was distinct from that of ace-1 [8].

Anatomical context of ace-1

• Based on the analysis of genetic mosaics, we conclude that in the absence of ace-2 and ace-3 function, the expression of ace-1(+) in muscle cells, but not in neurons, is essential for postembryonic viability [3].
• Significant decreases were detected in both SP immunoreactivity and AChE activity on days 6 and 10 postinfection (PI) in nematode-infected guinea pig jejunum compared to uninfected controls [9].

Associations of ace-1 with chemical compounds

• Acetylcholine (ACh) is one of an array of neurotransmitters used by invertebrates and, analogous to vertebrate nervous systems, acetylcholinesterase (AChE) regulates synaptic levels of this transmitter [10].
• Here, we describe the isolation and characterization of a cDNA encoding a putative neuromuscular AChE from D. viviparus which contains a tryptophan amphiphilic tetramerization (WAT) domain at its C-terminus analogous to the common 'tailed' AChE form found in the neuromuscular systems of vertebrates and in the ACE-1 AChE from Caenorhabditis elegans [10].
• As for the former enzyme, AChE C is truncated at the carboxyl terminus in comparison with the Torpedo AChE, and three of the 14 aromatic residues that line the active site gorge are substituted by nonaromatic residues, corresponding to Tyr70 (Ser), Trp279 (Asn) and Phe288 (Met) [11].
• In the first hour after antigen challenge with 0.5 mg nematode AChE there was a very sharp rise in Ch mainly from agonist-stimulated and phospholipase mediated phosphatidylcholine (PC) breakdown [12].

Regulatory relationships of ace-1

• A null mutation in ace-1 (allele p1000) suppresses all acetylcholinesterase activity of class A. We have identified an opal mutation TGG (W99)-->TGA (Stop) as the only alteration in the mutated gene [13].

Other interactions of ace-1

• cDNA sequence, gene structure, and in vitro expression of ace-1, the gene encoding acetylcholinesterase of class A in the nematode Caenorhabditis elegans [1].

Analytical, diagnostic and therapeutic context of ace-1

• The pattern of ace-1 expression was established through microinjection of Green Fluorescent Protein reporter gene constructs and showed a major mesodermal expression [14].
• Northern blot analysis indicated a progressive increase in mRNA for AChE B in parasites isolated from 6 days postinfection [15].
• The molecular weights of the AChE from the different species, estimated by gel filtration (Sephadex S300HR), ranged between 64 and 150 kDa [16].

References