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Conserved and divergent processing of neuroligin and neurexin genes: from the nematode C. elegans to human

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Invertebrate Neuroscience

Abstract

Neuroligins are cell-adhesion proteins that interact with neurexins at the synapse. This interaction may contribute to differentiation, plasticity and specificity of synapses. In humans, single mutations in neuroligin-encoding genes are implicated in autism spectrum disorder and/or mental retardation. Moreover, some copy number variations and point mutations in neurexin-encoding genes have been linked to neurodevelopmental disorders including autism. Neurexins are subject to extensive alternative splicing, highly regulated in mammals, with a great physiological importance. In addition, neuroligins and neurexins are subjected to proteolytic processes that regulate synaptic transmission modifying pre- and postsynaptic activities and may also regulate the remodelling of spines at specific synapses. Four neuroligin genes exist in mice and five in human, whilst in the nematode Caenorhabditis elegans, there is only one orthologous gene. In a similar manner, in mammals, there are three neurexin genes, each of them encoding two major isoforms named α and β, respectively. In contrast, there is one neurexin gene in C. elegans that also generates two isoforms like mammals. The complexity of the genetic organization of neurexins is due to extensive processing resulting in hundreds of isoforms. In this review, a wide comparison is made between the genes in the nematode and human with a view to better understanding the conservation of processing in these synaptic proteins in C. elegans, which may serve as a genetic model to decipher the synaptopathies underpinning neurodevelopmental disorders such as autism.

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Acknowledgments

I am very grateful to Lindy Holden-Dye and Vincent O’Connor for comments and critical reading of the manuscript. I also thank Lindy Holden-Dye, Vincent O’Connor and James Dillon for supervision, support and assistance. Suggestions and comments from Kathy-Ann Koralek are sincerely acknowledged.

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  1. Centre for Biological Sciences, University of Southampton, Life Sciences Building 85, Southampton, SO17 1BJ, UK

    Fernando Calahorro

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Calahorro, F. Conserved and divergent processing of neuroligin and neurexin genes: from the nematode C. elegans to human. Invert Neurosci 14, 79–90 (2014). https://doi.org/10.1007/s10158-014-0173-5

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