Neuroligin-deficient mutants of C. elegans have sensory processing deficits and are hypersensitive to oxidative stress and mercury toxicity
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SUMMARY: Neuroligins are postsynaptic cell adhesion proteins that bind specifically to presynaptic membrane proteins called neurexins. Mutations in human neuroligin genes are associated with autism spectrum disorders in some families. The nematode Caenorhabditis elegans has a single neuroligin gene (nlg-1), and approximately a sixth of C. elegans neurons, including some sensory neurons, interneurons and a subset of cholinergic motor neurons, express a neuroligin transcriptional reporter. Neuroligin-deficient mutants of C. elegans are viable, and they do not appear deficient in any major motor functions. However, neuroligin mutants are defective in a subset of sensory behaviors and sensory processing, and are hypersensitive to oxidative stress and mercury compounds; the behavioral deficits are strikingly similar to traits frequently associated with autism spectrum disorders. Our results suggest a possible link between genetic defects in synapse formation or function, and sensitivity to environmental factors in the development of autism spectrum disorders.
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Neuroligin-deficient mutants of C. elegans nematodes are hypersensitive to oxidative stress.
“a study has shown that neuroligin-deficient mutants of C. elegans nematodes are hypersensitive to oxidative stress.97”
From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [97]
Studies of animal models suggest that genetic defects in synaptic function may alter sensitivity to the environment.
“studies of animal models have suggested that genetic defects in synaptic function may alter sensitivity to the environment.”
From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [97]
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Autism risk factors: genes, environment, and gene-environment interactions
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Astrocytes close a motor circuit critical period
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Neurexin and Neuroligin Mediate Retrograde Synaptic Inhibition in C. elegans
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Genetic basis of autism: is there a way forward?
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Genome-wide expression studies in Autism spectrum disorder, Rett syndrome, and Down syndrome
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MADD-4/Punctin and Neurexin Organize C. elegans GABAergic Postsynapses through Neuroligin
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Neurexin directs partner-specific synaptic connectivity in C. elegans
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Neurexins and Neuroligins: Recent Insights from Invertebrates
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C. elegans Punctin Clusters GABAA Receptors via Neuroligin Binding and UNC-40/DCC Recruitment
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Self-citationMarques, R. C., Bernardi, J. V. E., Dorea, C. C., & Dórea, J. G. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17020577 · Cited by 57 · see citing works
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The neurexin superfamily of Caenorhabditis elegans
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Mechanisms and modifiers of methylmercury-induced neurotoxicity
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A network of autism linked genes stabilizes two pools of synaptic GABAA receptors
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Neuronal responses to stress and injury in C. elegans
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Are caesarean sections, induced labor and oxytocin regulation linked to Autism Spectrum Disorders?
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Staab, T. A., Egrafov, O., Knowles, J. A., & Sieburth, D. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004100 · Cited by 42 · see citing works
Role of NAD+, Oxidative Stress, and Tryptophan Metabolism in Autism Spectrum Disorders
Essa, M., Subash, S., Braidy, N., Al-Adawi, S., Lim, C. K., Manivasagam, T., & Guillemin, G. (2013) · International Journal of Tryptophan Research · doi:10.4137/ijtr.s11355 · Cited by 46 · see citing works
Directional Trans-Synaptic Labeling of Specific Neuronal Connections in Live Animals
Desbois, M., Cook, S. J., Emmons, S. W., & Bülow, H. E. (2015) · Genetics · doi:10.1534/genetics.115.177006 · Cited by 33 · see citing works
Koufaris, C., & Sismani, C. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16048699 · Cited by 32 · see citing works
Oliver, D., Ramachandran, S., Philbrook, A., Lambert, C. M., Nguyen, K. C. Q., Hall, D. H., & Francis, M. M. (2022) · PLoS Genetics · doi:10.1371/journal.pgen.1010016 · Cited by 31 · see citing works
Li, Y., Wang, Y., Hu, Y., Zhong, J.-X., & Wang, D. (2011) · Neuroscience Bulletin · doi:10.1007/s12264-011-1152-z · Cited by 31 · see citing works
Maglioni, S., Schiavi, A., Melcher, M., Brinkmann, V., Luo, Z., Laromaine, A., Raimundo, N., Meyer, J. N., Distelmaier, F., & Ventura, N. (2022) · Nature Communications · doi:10.1038/s41467-022-29972-4 · Cited by 30 · see citing works
Calahorro, F., & Ruiz‐Rubio, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039277 · Cited by 28 · see citing works
Synaptogenesis: unmasking molecular mechanisms using Caenorhabditis elegans
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Offenburger, S.-L., Jongsma, E., & Gartner, A. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007106 · Cited by 26 · see citing works
Worms on the spectrum - C. elegans models in autism research
Schmeißer, K., & Parker, J. A. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.04.007 · Cited by 23 · see citing works
Impact of drug solvents on C. elegans pharyngeal pumping
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Calahorro, F., & Ruiz‐Rubio, M. (2013) · Genes Brain & Behavior · doi:10.1111/gbb.12046 · Cited by 22 · see citing works
Etiology of autism spectrum disorders: Genes, environment, or both?
Shaw, C., Sheth, S. K. S., Li, D., & Tomljenovic, L. (2014) · Cited by 20 · see citing works
Conserved autism-associated genes tune social feeding behavior in C. elegans
Cowen, M. H., Haskell, D., Zoga, K., Reddy, K. C., Chalasani, S. H., & Hart, M. P. (2024) · Nature Communications · doi:10.1038/s41467-024-53590-x · Cited by 19 · see citing works
Molecular Architecture of Genetically-Tractable GABA Synapses in C. elegans
Zhou, X., & Bessereau, J. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00304 · Cited by 19 · see citing works
Neuroligin modulates the locomotory dopaminergic and serotonergic neuronal pathways of C. elegans
Izquierdo, P. G., Calahorro, F., & Ruiz‐Rubio, M. (2013) · Neurogenetics · doi:10.1007/s10048-013-0377-6 · Cited by 19 · see citing works
Gámez-del-Estal, M. M., Contreras, I., Prieto-Pérez, R., & Ruiz‐Rubio, M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00069 · Cited by 19 · see citing works
Wong, R. Y., & Cummings, M. E. (2014) · Brain Behavior and Evolution · doi:10.1159/000360071 · Cited by 19 · see citing works
Calahorro, F., Keefe, F., Dillon, J., Holden-Dye, L. M., & O'Connor, V. M. (2018) · Journal of Experimental Biology · doi:10.1242/jeb.189423 · Cited by 16 · see citing works
Recent advances in animal model experimentation in autism research
Tania, M., Khan, M. A., & Xia, K. (2013) · Acta Neuropsychiatrica · doi:10.1017/neu.2013.58 · Cited by 16 · see citing works
Rodríguez‐Ramos, Á., Gámez-del-Estal, M. M., Porta-de-la-Riva, M., Cerón, J., & Ruiz‐Rubio, M. (2017) · Behavior Genetics · doi:10.1007/s10519-017-9868-9 · Cited by 16 · see citing works
Rawsthorne, H., Calahorro, F., Feist, E., Holden-Dye, L. M., O'Connor, V. M., & Dillon, J. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa232 · Cited by 14 · see citing works
Rawsthorne, H., Calahorro, F., Holden-Dye, L. M., O'Connor, V. M., & Dillon, J. (2021) · PLoS ONE · doi:10.1371/journal.pone.0243121 · Cited by 13 · see citing works
Hippocampal and motor fronto-cortical neuroligin1 is increased in an animal model of depression
Feng, P., Akladious, A. A., & Hu, Y. (2016) · Psychiatry Research · doi:10.1016/j.psychres.2016.06.052 · Cited by 12 · see citing works
Functional mosaic organization of neuroligins in neuronal circuits
Qin, L., Guo, S., Han, Y., Wang, X., & Zhang, B. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03478-y · Cited by 11 · see citing works
Neuroligin-1 Is a Mediator of Methylmercury Neuromuscular Toxicity
Gunderson, J. T., Peppriell, A. E., Krout, I. N., Vorojeikina, D. P., & Rand, M. D. (2021) · Toxicological Sciences · doi:10.1093/toxsci/kfab114 · Cited by 11 · see citing works
Platsaki, S., Zhou, X., Pinan‐Lucarré, B., Delauzun, V., Tu, H., Mansuelle, P., Fourquet, P., Bourne, Y., Bessereau, J., & Marchot, P. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.014591 · Cited by 11 · see citing works
Zhang, Z., Hou, M., Ou, H., Wang, D., Li, Z., Zhang, H., & Lu, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1067529 · Cited by 9 · see citing works
Distinct mechanisms control the specific synaptic functions of Neuroligin 1 and Neuroligin 2
Wang, J., Südhof, T. C., & Wernig, M. (2025) · EMBO Reports · doi:10.1038/s44319-024-00286-4 · Cited by 9 · see citing works
Calahorro, F., Holden-Dye, L. M., & O'Connor, V. M. (2015) · Gene Expression Patterns · doi:10.1016/j.gep.2015.02.002 · Cited by 9 · see citing works
Calahorro, F. (2014) · Invertebrate Neuroscience · doi:10.1007/s10158-014-0173-5 · Cited by 9 · see citing works
Serum neopterin levels in patients with autism
Bodur, Ş., Ceylan, M. F., İşeri, E., Şener, Ş., & Yücel, A. A. (2013) · International Journal of Developmental Disabilities · doi:10.1179/2047387713y.0000000029 · Cited by 9 · see citing works
Persico, A. M. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-397267-5.00045-5 · Cited by 9 · see citing works
The Relevance of Caenorhabditis elegans Genetics for Understanding Human Psychiatric Disease
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Durand, N., Aguilar, P., Demondion, E., Bourgeois, T. P., Bozzolan, F., & Debernard, S. (2021) · Journal of Experimental Biology · doi:10.1242/jeb.243184 · Cited by 5 · see citing works
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C. elegans behavior, fitness, and lifespan, are modulated by AWB/ASH-dependent death perception
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Invertebrate Models of Synaptic Transmission in Autism Spectrum Disorders
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C. elegans behavior, fitness, and lifespan, are modulated by AWB/ASH-dependent death perceptionPreprint
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Inhibitory Synapses Get Madd for Neuroligin
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Genetic etiology and neurobiological mechanisms of autism spectrum disorders
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Ligand-Induced Cell Adhesion in Synapse Formation
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The Role of SAD-1 Kinase in Caenorhabditis elegans Neuronal Circuit Development and Function
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Susceptibility to Toxicants or Stresses Induced by Genetic Mutations
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Physiological and Pathological Models for Pharmacological Study
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Autism: epidemiology, genetics, molecular mechanisms, clinical features, diagnosis, and management
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- Authors
- Hunter, J. W., Mullen, G. P., McManus, J. R., Heatherly, J. M., Duke, A., & Rand, J. B.
- Affiliations
- Oklahoma Medical Research Foundation (US)
- Corresponding author
- Rand, James B.
- Venue
- Disease Models & Mechanisms
- Publisher
- The Company of Biologists
- Published
- 2010-04-28
- Volume
- 3
- Issue
- 5-6
- Pages
- 366-376
- ISSN
- 1754-8403 (ISSN-L)
- 1754-8411
- PMC
- PMC4068633
- OpenAlex
- W2146735224
- Cited by
- 86
- References
- 94
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 5 · 2020: 10 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 1 · 2015: 9 · 2014: 8 · 2013: 11 · 2012: 5
- FWCI
- 4.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Disease Models & Mechanisms (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Autism Speaks (AS1975)
- Ludwig Institute for Cancer Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- neuroligins, Caenorhabditis elegans, sensory processing deficits, sensory behavior, oxidative stress sensitivity, mercury toxicity, autism spectrum disorder, neurexin, synaptogenesis, environmental sensitivity
- MeSH terms
- Animals, Behavior, Animal, Cues, Humans, Mercury, Mutation, Neurons, Recombinant Fusion Proteins, Sensation, Synapses, Temperature, Biomarkers, Cell Adhesion Molecules, Neuronal, Caenorhabditis elegans, Sequence Homology, Amino Acid, Genes, Reporter, Oxidative Stress, Protein Transport, Muscle Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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