38th Annual Meeting of the Society for Invertebrate Pathology

Cadherin-like proteins located in the midgut epithelium of lepidopteran larvae function as receptors for Bacillus thuringiensis Cry1 toxins. The cadherin protein Bt-R_1a from Manduca sexta larvae is a receptor for the Cry1A family of toxins (Hua et al. 2004. Insect Biochem. Molec. Biol. 34: 193-202). We also determined that cadherin-repeat 12 (CR12) and the membrane proximal extracellular domain (MPED) as critical regions in BtR₁ for Cry1Ab binding and cytotoxicity (Hua et al. 2004. J. Biol. Chem. 279: 28051-28056). Binding to Bt-R₁ may cause conformational changes in Cry1Ab that lead to oligomerization, binding to aminopeptidase and finally membrane insertion (Bravo et al., 2004. Biochim. Biophys. Acta 1667:38-46). We report the discovery that CR12-MPED peptide produced in a heterologous system enhances the toxicity of Cry proteins towards target insects. Mixtures of CR12-MPED with Cry1Ab or Cry1Ac toxins fed to larvae increased Cry1A toxicity to M. sexta, Heliothis virenscens and Helicoverpa zea significantly. Apparently, toxin binding was not necessary for the enhancing effect, since radiolabeled CR12-MPED bound Cry1Ab but not Cry1Ac. Histochemistry results demonstrated that the CR12-MPED peptide induced Cry1Ab but not Cry1Ac aggregation. Possible mechanisms leading to Cry1A toxicity enhancement by CR12-MPED will be discussed.