The Role of a Dehalogenase in Drosophila Spermatogenesis

Johns Hopkins University, Baltimore MD

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Abstract

? DESCRIPTION (provided by applicant): Iodotyrosine deiodinase has long been ascribed to the task of iodide salvage in vertebrates as necessary for iodide homeostasis and synthesis of the iodinated hormone thyroxine. The presence of this enzyme was not expected in most other organisms since few are known to require iodide or produce thyroxine. Still, orthologs of the deiodinase have been discovered in all invertebrate genomes sequenced to date. Recently, their ability to promote deiodination has been confirmed by expressing and characterizing the enzyme from a series of representative organisms. The biological role of this enzyme in invertebrates is currently unknown but likely contributes to a previously unrecognized cell signaling system that represents a progenitor to the mammalian system based on thyroxine. Drosophila offers an expedient model for testing the significance of this enzyme and its halotyrosine substrates. Preliminary studies using RNAi have demonstrated the need for the deiodinase during spermatogenesis. Experiments are now proposed to correlate the enzyme's catalytic activity with fertility and fecundity. Disruption of sperm maturation will be visualized ith standard staining techniques available for tracking the morphological changes during development. Concurrent biochemical studies will determine the likely substrates in vivo and the enzymes responsible for their formation. Feeding studies will be used to recapitulate the results established by genetics and enzymology. Together, these investigations should establish the foundation for future development of small molecule inhibitors of the deiodinase to control insect populations.