The Role of a Dehalogenase in Drosophila Spermatogenesis

脱卤酶在果蝇精子发生中的作用

基本信息

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
项目类别：
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

项目摘要

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（由适用提供）：艾丁丁二碘酶长期以来一直归因于碘化物稳态的必要条件和碘化碘甲状腺素的合成所必需的碘化物拯救任务。在大多数其他生物体中，这种酶的存在不会被预期，因为已知很少有人需要碘或产生甲状腺素。尽管如此，在迄今为止测序的所有无脊椎动物基因组中仍发现了脱碘酶的直系同源物。最近，通过表达和表征来自一系列代表性组织的酶来确认它们的促进去二化的能力。该酶在无脊椎动物中的生物学作用目前尚不清楚，但可能有助于先前未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细胞。果蝇提供了一种方便模型，用于测试该酶及其卤代基底物的重要性。使用RNAi的初步研究表明，在精子发生过程中需要去二二肽酶。现在提出了将酶的催化活性与生育和繁殖力相关的实验。将可视化精子成熟的破坏ITH标准染色技术可用于跟踪发育过程中的形态变化。并发的生化研究将确定体内可能的底物和负责其形成的酶。喂养研究将用于概括遗传学和酶学确定的结果。这些投资共同为未来开发脱碘酶的小分子抑制剂的发展基础，以控制抑制人群。