Misregulation of bromotyrosine compromises fertility in male Drosophila

• 成果类型: Article
• 署名作者: Su, Qi; Xu, Bing; Chen, Xin; Rokita, Steven E.
• 署名单位: University of California System; University of California San Diego; Stanford University; Johns Hopkins University; Howard Hughes Medical Institute; Johns Hopkins University; Johns Hopkins University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12363
• DOI: 10.1073/pnas.2322501121
• 发表日期: 2024-05-21
• 关键词: iodotyrosine deiodinase; thyroid-hormones; protein; peroxidasin; tyrosine; iodine; actin; individualization; differentiation; identification

摘要

Biological regulation often depends on reversible reactions such as phosphorylation, acylation, methylation, and glycosylation, but rarely halogenation. A notable exception is the iodination and deiodination of thyroid hormones. Here, we report detection of bromotyrosine and its subsequent debromination during Drosophila spermatogenesis. Bromotyrosine is not evident when Drosophila express a native flavin- dependent dehalogenase that is homologous to the enzyme responsible for iodide salvage from iodotyrosine in mammals. Deletion or suppression of the dehalogenase- encoding condet (cdt) gene in Drosophila allows bromotyrosine to accumulate with no detectable chloro- or iodotyrosine. The presence of bromotyrosine in the cdt mutant males disrupts sperm individualization and results in decreased fertility. Transgenic expression of the cdt gene in late- staged germ cells rescues this defect and enhances tolerance of male flies to bromotyrosine. These results are consistent with reversible halogenation affecting Drosophila spermatogenesis in a process that had previously eluded metabolomic, proteomic, and genomic analyses.