DISRUPTION OF THE IP3 RECEPTOR GENE OF DROSOPHILA AFFECTS LARVAL METAMORPHOSIS AND ECDYSONE RELEASE

Background: The inositol 1,4,5-trisphosphate (IP3) receptor is an intr acellular calcium channel that couples cell membrane receptors, via th e second messenger IP3, to calcium signal transduction pathways within many types of cells, IP3 receptor function has been implicated in dev elopment, but the physiological processes affected by its function hav e yet to be elucidated. In order to identify these processes, we gener ated mutants in the IF3 receptor gene (itpr) of Drosophila and studied their phenotype during development. Results: All itpr mutant alleles were lethal. Lethality occurred primarily during the larval stages and was preceded by delayed moulting, insect moulting occurs in response to the periodic release of the steroid hormone ecdysone which, in Dros ophila, is synthesised and secreted by the ring gland, The observation of delayed moulting in the mutants, coupled with expression of the IP 3 receptor in the larval ring gland fed us to examine the effect of th e itpr alleles on ecdysone levels, On feeding ecdysone to mutant larva e, a partial rescue of the itpr phenotype was observed. In order to as sess ecdysone levels at all larval stages, we examined transcripts of an ecdysone-inducible gene, E74; these transcripts were downregulated in larvae expressing each of the itpr alleles. Conclusions: Our data s how that disruption of the Drosophila IP3 receptor gene leads to lower ed levels of ecdysone, Synthesis and release of ecdysone from the ring gland is thought to occur in response to a neurosecretory peptide hor mone secreted by the brain, We propose that this peptide hormone requi res an IP3 signalling pathway far ecdysone synthesis and release in Dr osophila and other insects. This signal transduction mechanism which l inks neuropeptide hormones to steroid hormone secretion might be evolu tionarily conserved.