Black widow spider venom (BWSV) kills Caenorhabditis elegans after injection owing to the presence of heat- and detergent-sensitive components, which are high-molecular-mass latrotoxins. A C. elegans homologue of latrophilin/CIRL (calcium-independent receptor for latrotoxin), B0457.1, was identified and shown to have five conserved domains. RNAi (RNA interference) of this gene rendered C. elegans resistant to BWSV, whereas RNAi for CYP37A1 or a neurexin I homologue, and a deletion mutant of the related B0286.2 gene, had no effect on BWSV toxicity. The latrophilin RNAi mutants exhibit changes in defaecation cycle and alterations in drug sensitivity. These results demonstrate that latrophilin mediates the toxicity of BWSV and provide evidence for a physiological function of this receptor.
- black widow spider
- Caenorhabditis elegans
- latrophilin/CIRL (calcium-independent receptor for latrotoxin)
↵1 Present address: Computational Genome Analysis Laboratory, ICRF, 44 Lincoln's Inn Fields, London WC2 A3PX, U.K.
↵2 Present address: School of Medicine, Department of Anatomy, University of Bristol, University Walk, Bristol BS8 1TD, U.K.
Abbreviations used: BWSV, black widow spider venom; dsRNA, double-stranded RNA; EST, expressed sequence tag; GPS, G-protein-coupled receptor protease cleavage site; LIT, latroinsectotoxin; LTX, latrotoxin; NGM, nematode growth medium; RNAi, RNA interference.
- The Biochemical Society, London ©2004