Abstract

The ability of iodotyrosine deiodinase to salvage iodide from iodotyrosine has long been recognized as critical for iodide homeostasis and proper thyroid function in vertebrates. The significance of its additional ability to dehalogenate bromo- and chlorotyrosine is less apparent, and none of these functions could have been anticipated in invertebrates until recently. Drosophila, as most arthropods, contains a deiodinase homolog encoded by CG6279, now named condet (cdt), with a similar catalytic specificity. However, its physiological role cannot be equivalent because Drosophila lacks a thyroid and its associated hormones, and no requirement for iodide or halotyrosines has been reported for this species. We have now applied CRISPR/Cas9 technology to generate Drosophila strains in which the cdt gene has been either deleted or mutated to identify its biological function. As previously shown in larvae, expression of cdt is primarily limited to the fat body, and we now report that loss of cdt function does not enhance sensitivity of the larvae to the toxic effects of iodotyrosine. In adult flies by contrast, expression is known to occur in testes and is detected at very high levels in this tissue. The importance of cdt is most evident in the decrease in fertility observed when either males or females carry a deletion or mutation of cdt Therefore, dehalogenation of a halotyrosine appears essential for efficient reproduction in Drosophila and likely contributes to a new pathway for controlling viability in arthropods.

Highlights

  • The flavoprotein iodotyrosine deiodinase (IYD)2 was discovered first in humans while studying the biochemical basis of thyroid disease [1, 2]

  • IYD is primarily expressed in the thyroid gland where this hormone is produced but it is expressed at lower levels in the digestive tract, kidney, and liver [3] where it may dehalogenate chloro- and bromotyrosine (Cl-Tyr, Br-Tyr) (Scheme 1) [4, 5]

  • The IYD gene was originally listed in flybase as CG6279 and has since been named condet, in honor of Dr Jean François Condet who discovered that ingestion of iodide could reduce goiter [15]

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Summary

The importance of a halotyrosine dehalogenase for Drosophila fertility

Abhishek Phatarphekar‡, Qi Su‡, Suk Ho Eun§, Xin Chen§, and Steven E. Rokita‡1 From the Departments of ‡Chemistry and §Biology, Johns Hopkins University, Baltimore, Maryland 21218

Edited by Ruma Banerjee
Generation of Drosophila strains with limited IYD activity in vivo
Expression of cdt in testes
Materials and methods
Larval feeding
Adult feeding
Fecundity after a limited mating period
In situ hybridization to identify cdt expression
Full Text
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