Article

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

Department of Zoology, University of Cambridge, Downing Street, Cambridge, CB2 3EJ, UK.
Invertebrate Neuroscience (Impact Factor: 1.19). 10/2007; 7(3):157-64. DOI: 10.1007/s10158-007-0051-5
Source: PubMed

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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