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Functional genomics of nematode acetylcholinesterases

Published online by Cambridge University Press:  29 March 2006

M. E. SELKIRK
Affiliation:
Division of Cell and Molecular Biology, Imperial College London, London SW7 2AY, United Kingdom
O. LAZARI
Affiliation:
Department of Veterinary Clinical Science, University of Liverpool, South Wirral, CH64 7TE, United Kingdom
J. B. MATTHEWS
Affiliation:
Division of Parasitology, Moredun Research Institute, Midlothian EH26 OPZ, United Kingdom

Abstract

Acetylcholine is the major excitatory neurotransmitter controlling motor activities in nematodes, and the enzyme which hydrolyses and inactivates acetylcholine, acetylcholinesterase, is thus essential for regulation of cholinergic transmission. Different forms of acetylcholinesterase are encoded by multiple genes in nematodes, and analysis of the pattern of expression of these genes in Caenorhabditis elegans suggests that they perform non-redundant functions. In addition, many parasitic species which colonise host mucosal surfaces secrete hydrophilic variants of acetylcholinesterase, although the function of these enzymes is still unclear. Acetylcholinesterases have a history as targets for therapeutic agents against helminth parasites, but anti-cholinesterases have been used much more extensively as pesticides, for example to control crop damage and ectoparasitic infestation of livestock. The toxicity associated with these compounds (generally organophosphates and carbamates) has led to legislation to withdraw them from the market or restrict their use in many countries. Nevertheless, acetylcholinesterases provide a good example of a neuromuscular target enzyme in helminth parasites, and it may yet be possible to develop more selective inhibitors. In this article, we describe what is known about the structure and function of vertebrate cholinesterases, illustrate the molecular diversity and tissue distribution of these enzymes in C. elegans, and discuss to what extent this may represent a paradigm for nematodes in general.

Type
Research Article
Copyright
2005 Cambridge University Press

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