Muscular dystrophy associated mutations in caveolin-1 induce neurotransmission and locomotion defects in Caenorhabditis elegans.
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.
Parker
Scott
S
Department of Zoology, University of Cambridge, Downing Street, Cambridge, CB2 3EJ, UK.
Peterkin
Helen S
HS
Baylis
Howard A
HA
D000818:Animals; D030801:Animals, Genetically Modified; D000969:Antinematodal Agents / Q000494:pharmacology; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D051242:Caveolin 1 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D034284:Dynamin I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007978:Levamisole / Q000494:pharmacology; D009068:Movement / Q000502:physiology*; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction
D000969:Antinematodal Agents; D029742:Caenorhabditis elegans Proteins; D051242:Caveolin 1; C495538:cav-1 protein, C elegans; D007978:Levamisole; D034284:Dynamin I