DISRUPTION OF LYSOSOMAL TARGETING IS ASSOCIATED WITH INSECTICIDAL POTENCY OF JUVENILE-HORMONE ESTERASE

Juvenile hormone esterase (JHE; EC, 3.1.1.1), which is intrinsically i nvolved in regulation of development of some insect larvae, is rapidly removed from the hemolymph by the pericardial cells, Lys-29 and Lys-5 24, which are implicated in the degradation of JHE, were mutated to Ar g, Neither the half-life of the modified JHE in the hemolymph nor the catalytic parameters were changed significantly, but when combined, th ese mutations resulted in apparent failure of lysosomal targeting in t he pericardial cell complex, A hypothesis for the mechanism of reduced efficiency of lysosomal targeting is presented, Infection of larvae w ith a recombinant baculovirus expressing the modified JHE resulted in a 50% reduction in feeding damage compared with larvae infected with t he wild-type virus, thus demonstrating improved properties as a biolog ical insecticide, These data demonstrate that alteration of specific r esidues of JHE that disrupted lysosomal targeting, dramatically increa sed the insecticidal activity of this protein.