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Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour and are functional orthologues of Haemonchus contortus receptors

Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour and are functional orthologues of Haemonchus contortus receptors
Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour and are functional orthologues of Haemonchus contortus receptors
The target site for the anthelmintic action of ivermectin is a family of nematode glutamate-gated chloride channel alpha subunits (GluClalpha) that bind the drug with high affinity and mediate its potent paralytic action. Whilst the action of ivermectin on the pharyngeal muscle of nematodes is relatively well understood, its effect on locomotor activity is less clear. Here we use RNAi and gene knockouts to show that four GluClalpha subunits are involved in regulating the pattern of locomotor activity in Caenorhabditis elegans. A Haemonchus contortus orthologue of these subunits, HcGluClalpha3, has been shown to be expressed in the motor nervous system and here we have shown that it is a functional, as well as a structural, orthologue by virtue of the observation that it can restore normal motor movement in the C. elegans GluClalpha mutant, avr-14(ad1032), when expressed under the control of the avr-14 promoter. This supports the contention that ivermectin exerts its paralytic action on parasitic nematodes through activation of GluCl channels in the motor nervous system. Furthermore, functional complementation in C. elegans provides a method to further the understanding of this important class of anthelmintic targets.
glutamate-gated chloride channels, nematode, anthelmintic, ivermectin
0166-6851
118-125
Cook, Alan
7b75a288-b189-4c85-8122-0f389847ac4a
Aptel, Nathalie
237ab896-5cbe-4a3e-b9ee-97a9e2ae9811
Portillo, Virginia
770c2877-6085-4322-8637-405abaf2252d
Siney, Elodie
8be7cefb-b63f-4c92-a275-b0495e75e4b2
Sihota, Rajinder
8cb19ebf-352e-484c-aec4-cf55fa670e47
Holden-Dye, Lindy
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Wolstenholme, Adrian
1b90606b-053e-408e-95a8-8b4f3dee75be
Cook, Alan
7b75a288-b189-4c85-8122-0f389847ac4a
Aptel, Nathalie
237ab896-5cbe-4a3e-b9ee-97a9e2ae9811
Portillo, Virginia
770c2877-6085-4322-8637-405abaf2252d
Siney, Elodie
8be7cefb-b63f-4c92-a275-b0495e75e4b2
Sihota, Rajinder
8cb19ebf-352e-484c-aec4-cf55fa670e47
Holden-Dye, Lindy
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Wolstenholme, Adrian
1b90606b-053e-408e-95a8-8b4f3dee75be

Cook, Alan, Aptel, Nathalie, Portillo, Virginia, Siney, Elodie, Sihota, Rajinder, Holden-Dye, Lindy and Wolstenholme, Adrian (2006) Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour and are functional orthologues of Haemonchus contortus receptors. Molecular and Biochemical Parasitology, 147 (1), 118-125. (doi:10.1016/j.molbiopara.2006.02.003).

Record type: Article

Abstract

The target site for the anthelmintic action of ivermectin is a family of nematode glutamate-gated chloride channel alpha subunits (GluClalpha) that bind the drug with high affinity and mediate its potent paralytic action. Whilst the action of ivermectin on the pharyngeal muscle of nematodes is relatively well understood, its effect on locomotor activity is less clear. Here we use RNAi and gene knockouts to show that four GluClalpha subunits are involved in regulating the pattern of locomotor activity in Caenorhabditis elegans. A Haemonchus contortus orthologue of these subunits, HcGluClalpha3, has been shown to be expressed in the motor nervous system and here we have shown that it is a functional, as well as a structural, orthologue by virtue of the observation that it can restore normal motor movement in the C. elegans GluClalpha mutant, avr-14(ad1032), when expressed under the control of the avr-14 promoter. This supports the contention that ivermectin exerts its paralytic action on parasitic nematodes through activation of GluCl channels in the motor nervous system. Furthermore, functional complementation in C. elegans provides a method to further the understanding of this important class of anthelmintic targets.

Full text not available from this repository.

More information

Published date: 24 February 2006
Keywords: glutamate-gated chloride channels, nematode, anthelmintic, ivermectin

Identifiers

Local EPrints ID: 40528
URI: http://eprints.soton.ac.uk/id/eprint/40528
ISSN: 0166-6851
PURE UUID: 34f98b6f-eab8-4df9-b669-5e783a917407
ORCID for Lindy Holden-Dye: ORCID iD orcid.org/0000-0002-9704-1217

Catalogue record

Date deposited: 03 Jul 2006
Last modified: 10 Dec 2019 01:59

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