Impaired Dopamine-Dependent Locomotory Behavior of C. elegans Neuroligin Mutants Depends on the Catechol-O-Methyltransferase COMT-4

Abstract

Neurexins and neuroligins are neuronal membrane adhesion molecules that have been involved in neuropsychiatric and neurodevelopmental disorders. The nrx-1 and nlg-1 genes of Caenorhabditis elegans encode NRX-1 and NLG-1, orthologue proteins of human neurexins and neuroligins, respectively. Dopaminergic and serotoninergic signalling control the locomotory rate of the nematode. When well-fed animals are transferred to a plate with food (bacterial lawn), they reduce the locomotory rate. This behavior, which depends on dopamine, is known as basal slowing response (BSR). Alternatively, when food-deprived animals are moved to a plate with a bacterial lawn, further decrease their locomotory rate. This behavior, known as enhanced slowing response (ESR), is serotonin dependent. C. elegans nlg-1-deficient mutants are impaired in BSR and ESR. Here we report that nrx-1-deficient mutants were defective in ESR, but not in BSR. The nrx-1;nlg-1 double mutant was impaired in both behaviors. Interestingly, the nlg-1 mutants upregulate the expression of comt-4 which encodes an enzyme with putative catechol-O-methyltransferase activity involved in dopamine degradation. Our study also shows that comt-4(RNAi) in nlg-1-deficient mutants rescues the wild type phenotypes of BSR and ESR. On the other hand, comt-4(RNAi) in nlg-1-deficient mutants also recovers, at least partially, the gentle touch response and the pharyngeal pumping rate that were impaired in these mutants. These latter behaviors are dopamine and serotonin dependent, respectively. Based on these results we propose a model for the neuroligin function in modulating the dopamine-dependent locomotory behavior in the nematode.

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Acknowledgements

We thank Caenorhabditis Genetic Center (University of Minnesota, USA) and the Japanese National Bioresource Project, for worm strains. We also thank María Vargas Soria for her help in the pharyngeal pumping rate experiments, Mónica Pérez Alegre y Eloísa Andújar Pulido from the Genomic Unit of CABIMER (Sevilla, Spain) for technical and bioinformatic analysis support, Peter Askjaer (CABD, Sevilla, Spain) for providing us with HT115 E. coli strain (DE3) with plasmid pL4440 carrying unc-22 gene fragment, and José Manuel Moreno Ventura for critical reading of the manuscript.

Funding

The research work was supported by grants ITC-20111029 (Centro para el Desarrollo Tecnológico e Industrial, Spain) and “Plan Propio de Investigación de la Universidad de Córdoba”, Spain.

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Correspondence to Manuel Ruiz-Rubio.

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Ángel Rodríguez-Ramos, M. Mar Gámez-del-Estal, Montserrat Porta-de-la-Riva, Julián Cerón and Manuel Ruiz-Rubio declare that they have no conflict of interest.

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All experiments were performed with Caenorhabditis elegans and the nematode is free of ethical concern.

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This article only contains experiments using the Caenorhabditis elegans. All international, national, and/or institutional guidelines consider that this nematode is free of ethical concern.

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No human data or sample were used in this study and informed consent is not required.

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Edited by Charalambos Kyriacou.

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Rodríguez-Ramos, Á., Gámez-del-Estal, M.M., Porta-de-la-Riva, M. et al. Impaired Dopamine-Dependent Locomotory Behavior of C. elegans Neuroligin Mutants Depends on the Catechol-O-Methyltransferase COMT-4. Behav Genet 47, 596–608 (2017). https://doi.org/10.1007/s10519-017-9868-9

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Keywords

  • Locomotor behavior
  • Neuroligin
  • Neurexin
  • Dopamine
  • Serotonin
  • Catechol-O-methyltransferase
  • RNAi
  • Caenorhabditis elegans