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The evolution of pentameric ligand-gated ion-channels and the changing family of anthelmintic drug targets

Published online by Cambridge University Press:  30 October 2014

ROBIN N. BEECH  and
CÉDRIC NEVEU
ROBIN N. BEECH*
Affiliation:
French National Institute for Agricultural Research (INRA), UR1282 Infectiologie Animale et santé Publique, Nouzilly F-37380, France Institute of Parasitology, Macdonald Campus, McGill University, 21,111 Lakeshore Road, Ste Anne de Bellevue, Quebec H9X 3V9, Canada
CÉDRIC NEVEU
Affiliation:
French National Institute for Agricultural Research (INRA), UR1282 Infectiologie Animale et santé Publique, Nouzilly F-37380, France
*
* Corresponding author: French National Institute for Agricultural Research (INRA), Infectiologie Animale et santé Publique, Nouzilly, France. E-mail: [email protected]
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Summary

Pentameric ligand-gated ion-channels rapidly transduce synaptic neurotransmitter signals to an electrical response in post-synaptic neuronal or muscle cells and control the neuromusculature of a majority of multicellular animals. A wide range of pharmaceuticals target these receptors including ethanol, nicotine, anti-depressants and other mood regulating drugs, compounds that control pain and mobility and are targeted by a majority of anthelmintic drugs used to control parasitic infection of humans and livestock. Major advances have been made in recent years to our understanding of the structure, function, activity and the profile of compounds that can activate specific receptors. It is becoming clear that these anthelmintic drug targets are not fixed, but differ in significant details from one nematode species to another. Here we review what is known about the evolution of the pentameric ligand-gated ion-channels, paying particular attention to the nematodes, how we can infer the origins of such receptors and understand the factors that determine how they change both over time and from one species to another. Using this knowledge provides a biological framework in which to understand these important drug targets and avenues to identify new receptors and aid the search for new anthelmintic drugs.

Keywords

pentameric ligand-gated ion-channelsgene duplicationgene lossreceptor compositionneurotransmitteranthelmintic target
Type
Review Article
Information
Parasitology , Volume 142 , Issue 2 , February 2015 , pp. 303 - 317
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Copyright
Copyright © Cambridge University Press 2014 

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