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Whole-genome analysis of 60 G protein-coupled receptors in Caenorhabditis elegans by gene knockout with RNAi

Whole-genome analysis of 60 G protein-coupled receptors in Caenorhabditis elegans by gene knockout with RNAi
Whole-genome analysis of 60 G protein-coupled receptors in Caenorhabditis elegans by gene knockout with RNAi
G protein-coupled receptors (GPCRs) are the largest family of genes in animal genomes and represent more than 2% of genes in humans and C. elegans. These evolutionarily conserved seven-transmembrane proteins transduce a diverse range of signals. In view of their pivotal role in cell signaling, it is perhaps surprising that decades of genetic analysis in C. elegans, and recent genome-wide RNAi screens, have identified very few GPCR mutants [1 and 2]. Therefore, we screened all GPCRs predicted to bind either small-molecule neurotransmitters or neuropeptides by using RNAi and quantitative behavioral assays. This shows that C16D6.2, C25G6.5, C26F1.6, F35G8.1, F41E7.3, and F59C12.2 are likely to be involved in reproduction, whereas C15B12.5, C10C6.2, C24A8.4, F15A8.5, F59D12.1, T02E9.1, and T05A1.1 have a role in locomotion. Gene deletions for F35G8.1 and T05A1.1 resulted in the same phenotype as that seen with RNAi. As some GPCRs may be resistant to RNAi, or may result in abnormalities not screened for here, the actual proportion of nonredundant receptors with an assayable function is probably greater. Strikingly, most phenotypes were observed for NPY-like receptors that may bind neuropeptides. This is consistent with the known actions of neuropeptides on the body wall muscle and reproductive tract in nematodes [3, 4 and 5].
0960-9822
1715-1720
Keating, C.D.
24eb44a2-a6bc-42df-9993-ca2cd4cfbbc8
Kriek, N.
2be7a156-d337-4337-bf8d-5e782d87d8df
Daniels, M.
e3984a06-3c8f-4ac6-8a0d-f7824fc3cd22
Ashcroft, N.R.
4e59c3cb-40d0-443b-abe1-653147dcbd77
Hopper, N.A.
ddc67e10-c632-4400-9b27-a93de6baabd7
Siney, E.J.
8be7cefb-b63f-4c92-a275-b0495e75e4b2
Holden-Dye, L.
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Burke, J.F.
8ac5c1c4-98fb-4198-b7e6-77c3baefe3f8
Keating, C.D.
24eb44a2-a6bc-42df-9993-ca2cd4cfbbc8
Kriek, N.
2be7a156-d337-4337-bf8d-5e782d87d8df
Daniels, M.
e3984a06-3c8f-4ac6-8a0d-f7824fc3cd22
Ashcroft, N.R.
4e59c3cb-40d0-443b-abe1-653147dcbd77
Hopper, N.A.
ddc67e10-c632-4400-9b27-a93de6baabd7
Siney, E.J.
8be7cefb-b63f-4c92-a275-b0495e75e4b2
Holden-Dye, L.
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Burke, J.F.
8ac5c1c4-98fb-4198-b7e6-77c3baefe3f8

Keating, C.D., Kriek, N., Daniels, M., Ashcroft, N.R., Hopper, N.A., Siney, E.J., Holden-Dye, L. and Burke, J.F. (2003) Whole-genome analysis of 60 G protein-coupled receptors in Caenorhabditis elegans by gene knockout with RNAi. Current Biology, 13 (19), 1715-1720. (doi:10.1016/j.cub.2003.09.003).

Record type: Article

Abstract

G protein-coupled receptors (GPCRs) are the largest family of genes in animal genomes and represent more than 2% of genes in humans and C. elegans. These evolutionarily conserved seven-transmembrane proteins transduce a diverse range of signals. In view of their pivotal role in cell signaling, it is perhaps surprising that decades of genetic analysis in C. elegans, and recent genome-wide RNAi screens, have identified very few GPCR mutants [1 and 2]. Therefore, we screened all GPCRs predicted to bind either small-molecule neurotransmitters or neuropeptides by using RNAi and quantitative behavioral assays. This shows that C16D6.2, C25G6.5, C26F1.6, F35G8.1, F41E7.3, and F59C12.2 are likely to be involved in reproduction, whereas C15B12.5, C10C6.2, C24A8.4, F15A8.5, F59D12.1, T02E9.1, and T05A1.1 have a role in locomotion. Gene deletions for F35G8.1 and T05A1.1 resulted in the same phenotype as that seen with RNAi. As some GPCRs may be resistant to RNAi, or may result in abnormalities not screened for here, the actual proportion of nonredundant receptors with an assayable function is probably greater. Strikingly, most phenotypes were observed for NPY-like receptors that may bind neuropeptides. This is consistent with the known actions of neuropeptides on the body wall muscle and reproductive tract in nematodes [3, 4 and 5].

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Submitted date: 24 February 2003
Published date: 30 September 2003
Organisations: Biological Sciences

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Local EPrints ID: 26686
URI: http://eprints.soton.ac.uk/id/eprint/26686
ISSN: 0960-9822
PURE UUID: 4412171b-13ab-4252-8b32-afdd55680cbb
ORCID for L. Holden-Dye: ORCID iD orcid.org/0000-0002-9704-1217

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Date deposited: 10 Apr 2006
Last modified: 16 Mar 2024 02:35

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Contributors

Author: C.D. Keating
Author: N. Kriek
Author: M. Daniels
Author: N.R. Ashcroft
Author: N.A. Hopper
Author: E.J. Siney
Author: L. Holden-Dye ORCID iD
Author: J.F. Burke

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