The Role of a Dehalogenase in Drosophila Spermatogenesis

 说明(申请人提供)：长期以来，碘酪氨酸脱碘酶一直被认为是脊椎动物回收碘的任务，是维持碘的动态平衡和合成碘化激素甲状腺激素所必需的。这种酶的存在在大多数其他生物中是没有预料到的，因为很少有已知的生物需要碘或产生甲状腺素。然而，到目前为止，在所有已测序的无脊椎动物基因组中都发现了脱碘酶的同源基因。最近，通过表达和鉴定一系列具有代表性的生物体的酶，证实了它们促进脱碘的能力。这种酶在无脊椎动物中的生物学作用目前尚不清楚，但可能参与了以前未被识别的细胞信号系统，该系统代表了以甲状腺激素为基础的哺乳动物系统的前体。果蝇为测试这种酶及其卤代酪氨酸底物的重要性提供了一个便利的模型。使用RNAi的初步研究表明，在精子发生过程中需要脱碘酶。现在有人提议进行实验，将这种酶的催化活性与生育能力和繁殖力联系起来。精子成熟的破坏将通过可用于跟踪发育过程中的形态变化的标准染色技术来可视化。同时进行的生化研究将确定体内可能的底物以及负责它们形成的酶。饲养研究将被用来概括遗传学和酶学所确定的结果。总而言之，这些研究应该为未来开发小分子脱碘酶抑制剂来控制昆虫种群奠定基础。

 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.