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Muscular dystrophy associated mutations in caveolin-1 induce neurotransmission and locomotion defects in Caenorhabditis elegans

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Invertebrate Neuroscience

Abstract

Mutations in human caveolin-3 are known to underlie a range of myopathies. The cav-1 gene of Caenorhabditis elegans is a homologue of human caveolin-3 and is expressed in both neurons and body wall muscles. Within the body wall muscle CAV-1 localises adjacent to neurons, most likely at the neuromuscular junction (NMJ). Using fluorescently tagged CAV-1 and pre- and post-synaptic markers we demonstrate that CAV-1 co-localises with UNC-63, a post-synaptic marker, but not with several pre-synaptic markers. To establish a model for human muscular dystrophies caused by dominant-negative mutations in caveolin-3 we created transgenic animals carrying versions of cav-1 with homologous mutations. These animals had increased sensitivity to levamisole, suggesting a role for cav-1 at the NMJ. Animals carrying a deletion in cav-1 show a similar sensitivity. Sensitivity to levamisole and locomotion were also perturbed in animals carrying a dominant-negative cav-1 and a mutation in dynamin, which is a protein known to interact with caveolins. Thus, indicating an interaction between CAV-1 and dynamin at the NMJ and/or in neurons.

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Acknowledgments

We are grateful to Jeremy Skepper for advice on dual colour imaging. We are grateful to Jean-Louis Bessereau for plasmid pJL37 and Andrew Fire for transgenic expression vectors. Some strains were obtained from the Caenorhabditis Genetic Centre. This work was supported by the BBSRC (SP and HP). HAB is an MRC Senior Fellow.

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  1. Scott Parker

    Present address: Department of Molecular Microbiology and Immunology, Saint Louis University Medical School, 1402 South Grand Blvd, St Louis, MO, 63104, USA

Authors and Affiliations

  1. Department of Zoology, University of Cambridge, Downing Street, Cambridge, CB2 3EJ, UK

    Scott Parker, Helen S. Peterkin & Howard A. Baylis

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  1. Scott Parker
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Correspondence to Howard A. Baylis.

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Parker, S., Peterkin, H.S. & Baylis, H.A. Muscular dystrophy associated mutations in caveolin-1 induce neurotransmission and locomotion defects in Caenorhabditis elegans . Invert Neurosci 7, 157–164 (2007). https://doi.org/10.1007/s10158-007-0051-5

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