The Role of a Dehalogenase in Drosophila Spermatogenesis

脱卤酶在果蝇精子发生中的作用

• 批准号: 8952629
• 负责人: STEVEN E ROKITA
• 金额: $ 23.42万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8952629
• 关键词: Affinity; Amitrole; Anabolism; Antibodies; Biochemical; Biological; Bromides; Catalytic Domain; Chloride Ion; Chlorides; Chordata; Collagen; Complement; Complement Suppression; Databases; Detection; Development; Diet; Disease; Dissociation; Drosophila genus; Drosophila melanogaster; Enzymatic Biochemistry; Enzymes; Exposure to; Fertility; Foundations; Future; Generations; Genes; Genetic; Goals; Green Fluorescent Proteins; Homeostasis; Hormones; Human; Hydrogen Peroxide; Image; In Situ Hybridization; In Vitro; Insect Control; Insecta; Invertebrates; Investigation; Iodide Peroxidase; Iodides; Logic; Mammals; Measures; Metabolism; Modeling; Monoiodotyrosine; Nutritional Requirements; Organism; Orthologous Gene; Peroxidases; Phenotype; Population; Population Control; Process; Propylthiouracil; Proteins; RNA Interference; Regulation; Role; Series; Signal Pathway; Signal Transduction; Site; Somatic Cell; Specificity; Sperm Maturation; Spermatocytes; Spermatogenesis; Staging; Staining method; Stains; Study models; System; Techniques; Technology; Testing; Thiourea; Thyroid Function Tests; Thyroxine; Tyrosine; Vector-transmitted infectious disease; Vertebrates; analog; base; crosslink; dehalogenation; deiodination; dietary supplements; feeding; genome sequencing; halogenation; heme a; in vivo; inhibitor/antagonist; invertebrate genome; male; mutant; overexpression; progenitor; public health relevance; research study; small molecule; sperm cell; success; time use

 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.

 描述（由申请人提供）：长期以来，碘酪氨酸脱碘酶一直被认为负责脊椎动物中碘化物回收的任务，这是碘化物稳态和碘化激素甲状腺素合成所必需的。大多数其他生物体中不会存在这种酶，因为已知很少有生物体需要碘化物或产生甲状腺素。尽管如此，迄今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直系同源物。最近，通过表达和表征一系列代表性生物体的酶，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，但可能有助于形成以前未被识别的细胞信号系统，该系统代表基于甲状腺素的哺乳动物系统的祖先。果蝇提供了一个方便的模型来测试这种酶及其卤代酪氨酸底物的重要性。使用 RNAi 的初步研究表明精子发生过程中需要脱碘酶。现在建议进行实验将该酶的催化活性与生育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其形成的酶。喂养研究将用于概括遗传学和酶学建立的结果。总之，这些研究应该为未来开发用于控制昆虫种群的脱碘酶小分子抑制剂奠定基础。