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Human alpha- and beta-NRXN1 isoforms rescue behavioral impairments of caenorhabditis elegans neurexin-deficient mutants

Human alpha- and beta-NRXN1 isoforms rescue behavioral impairments of caenorhabditis elegans neurexin-deficient mutants
Human alpha- and beta-NRXN1 isoforms rescue behavioral impairments of caenorhabditis elegans neurexin-deficient mutants
Neurexins are cell adhesion proteins that interact with neuroligin and other ligands at the synapse. In humans, mutations in neurexin or neuroligin genes have been associated with autism and other mental disorders. The human neurexin and neuroligin genes are orthologous to the Caenorhabditis elegans genes nrx-1 and nlg-1, respectively. Here we show that nrx-1-deficient mutants are defective in exploratory capacity, sinusoidal postural movements and gentle touch response. Interestingly, the exploratory behavioral phenotype observed in nrx-1 mutants was markedly different to nlg-1-deficient mutants; thus, while the former had a 'hyper-reversal' phenotype increasing the number of changes of direction with respect to the wild-type strain, the nlg-1 mutants presented a 'hypo-reversal' phenotype. On the other hand, the nrx-1- and nlg-1-defective mutants showed similar abnormal sinusoidal postural movement phenotypes. The response of these mutant strains to aldicarb (acetylcholinesterase inhibitor), levamisole (ACh agonist) and pentylenetetrazole [gamma-aminobutyric (GABA) receptor antagonist], suggested that the varying behavioral phenotypes were caused by defects in ACh and/or GABA inputs. The defective behavioral phenotypes of nrx-1-deficient mutants were rescued in transgenic strains expressing either human alpha- or beta-NRXN-1 isoforms under the worm nrx-1 promoter. A previous report had shown that human and rat neuroligins were functional in C. elegans. Together, these results suggest that the functional mechanism underpinning both neuroligin and neurexin in the nematode are comparable to human. In this sense the nematode might constitute a simple in vivo model for understanding basic mechanisms involved in neurological diseases for which neuroligin and neurexin are implicated in having a role
1601-1848
453-464
Calahorro, F.
dddfa373-d3cc-433f-8851-9ca37f2f3950
Ruiz-Rubio, M.
ee8caed2-2cf8-486b-923b-b2bb83371d33
Calahorro, F.
dddfa373-d3cc-433f-8851-9ca37f2f3950
Ruiz-Rubio, M.
ee8caed2-2cf8-486b-923b-b2bb83371d33

Calahorro, F. and Ruiz-Rubio, M. (2013) Human alpha- and beta-NRXN1 isoforms rescue behavioral impairments of caenorhabditis elegans neurexin-deficient mutants. Genes, Brain, and Behavior, 12 (4), 453-464. (doi:10.1111/gbb.12046). (PMID:23638761)

Record type: Article

Abstract

Neurexins are cell adhesion proteins that interact with neuroligin and other ligands at the synapse. In humans, mutations in neurexin or neuroligin genes have been associated with autism and other mental disorders. The human neurexin and neuroligin genes are orthologous to the Caenorhabditis elegans genes nrx-1 and nlg-1, respectively. Here we show that nrx-1-deficient mutants are defective in exploratory capacity, sinusoidal postural movements and gentle touch response. Interestingly, the exploratory behavioral phenotype observed in nrx-1 mutants was markedly different to nlg-1-deficient mutants; thus, while the former had a 'hyper-reversal' phenotype increasing the number of changes of direction with respect to the wild-type strain, the nlg-1 mutants presented a 'hypo-reversal' phenotype. On the other hand, the nrx-1- and nlg-1-defective mutants showed similar abnormal sinusoidal postural movement phenotypes. The response of these mutant strains to aldicarb (acetylcholinesterase inhibitor), levamisole (ACh agonist) and pentylenetetrazole [gamma-aminobutyric (GABA) receptor antagonist], suggested that the varying behavioral phenotypes were caused by defects in ACh and/or GABA inputs. The defective behavioral phenotypes of nrx-1-deficient mutants were rescued in transgenic strains expressing either human alpha- or beta-NRXN-1 isoforms under the worm nrx-1 promoter. A previous report had shown that human and rat neuroligins were functional in C. elegans. Together, these results suggest that the functional mechanism underpinning both neuroligin and neurexin in the nematode are comparable to human. In this sense the nematode might constitute a simple in vivo model for understanding basic mechanisms involved in neurological diseases for which neuroligin and neurexin are implicated in having a role

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Published date: June 2013
Organisations: Biomedicine

Identifiers

Local EPrints ID: 366692
URI: https://eprints.soton.ac.uk/id/eprint/366692
ISSN: 1601-1848
PURE UUID: 7e9f0f2f-110c-41a5-bf5a-3c4aa0bd5b84
ORCID for F. Calahorro: ORCID iD orcid.org/0000-0003-0659-7728

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Date deposited: 10 Jul 2014 11:07
Last modified: 01 Oct 2019 00:36

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