AaIT: From neurotoxin to insecticide

AaIT is a single chain neurotoxic polypeptide derived from the venom of the Buthid scorpion Androctonus australis Hector, composed of 70 amino acids c ross-linked by four disulfide bridges. Its strict selectivity for insects h as been documented by toxicity, electrophysiological and ligand receptor bi nding assays. These last have shown that various insect neuronal membranes possess a single class of non-interacting AaIT binding sites of high affini ty (K-D = 1-3(n)M) and low capacity (0.5-2.0 pmol/mg prot.). The fast excit atory paralysis induced by AaIT is a result of a presynaptic effect, namely the induction of a repetitive firing in the terminal branches of the insec t's motor nerves resulting in a massive and uncoordinated stimulation of th e respective skeletal muscles. The neuronal repetitive activity is attribut ed to an exclusive and specific perturbation of sodium conductance as a con sequence of toxin binding to external loops of the insect voltage-dependent sodium channel and modification of its gating mechanism. From a strictly a grotechnical point of view AaIT involvement in plant protection has taken t he following two complementary forms: firstly, as a factor for the genetic engineering of insect infective baculoviruses resulting in potent and selec tive bio-insecticides. The efficacy of the AaIT-expressing, recombinant bac ulovirus is attributed mainly to its ability to continuously provide and tr anslocate the gene of the expressed toxin to the insect central nervous sys tem; secondly, based on the pharmacological flexibility of the voltage-gate d sodium channel, as a device for insecticide resistance management. Channe l mutations conferring resistance to a given class of insecticidal agents ( such as the KDR phenomenon) may greatly increase susceptibility to the AaIT expressing bioinsecticides. Thus the AaIT is a pharmacological tool for th e study of insect neuronal excitability and chemical ecology and the develo pment of new approaches to insect control. (C) 2000 Societe francaise de bi ochimie et biologie moleculaire / Editions scientifiques et medicales Elsev ier SAS.