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United States Department of Agriculture

Agricultural Research Service

Research Project: CHEMICAL BIOLOGY OF INSECT AND PLANT SIGNALING SYSTEMS

Location: Chemistry Research Unit

Title: RXR function requires binding to an endogenous terpenoid ligand

Authors
item Jones, Grace -
item Jones, Davy -
item Teal, Peter
item Henrich, Vincent -
item Sapa, Agnes -
item Krzywonos, Anna -
item Wozniak, Mietek -

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: June 3, 2013
Publication Date: N/A

Technical Abstract: The issue of whether the nuclear receptor RXR must bind to an endogenous, nanomolar affinity ligand in order to perform its natural function is still unsettled (1). On the basis of our previous studies establishing that the Drosophilamelanogaster ortholog of the retinoid X receptor ("ultraspiracle," USP) has nanomolar affinity for methyl farnesoate (2), residues in the USP ligand binding pocket were mutated to reduce binding affinity for methyl farnesoate. Transgenic wild type USP, or the mutant USP, were expressed in a null USP background, under the control of the natural USP promoter. The early larval lethality of the null USP background was rescued through metamorphic transition to the pupal and adult form by the transgenic wild type USP. However, USP with a debilitated ligand binding pocket was unable to sustain proper morphogenetic development through the larval to pupal transition. This in vivo functional assay of RXR (USP) ligand binding function appears appropriate for evaluation of USPmediated hormonal networks in some medically important vectors of disease, as a transgenic mosquito (Aedes aegypti) USP, driven by the above promoter, was also able to rescue larval Drosophila development to the adult form. From the hormone direction, RNAi-mediated disruption of proper ring gland biosynthesis of methyl farnesoate also disrupted the same morphogenetic transition point. We also determined that a related model dipteran (Musca domestica), treatment with a metabolically stabilized methyl farnesoate derivative (3) also disrupted this morphogenetic transition. These data indicate that the morphogenetic progression from the immature to the mature form in these model systems requires the involvement of a distinct endocrine axis of USP binding, in a developmentally controlled manner, to an endogenous terpenoid ligand. This hormone/receptor axis is distinct from, but intersects with, insect hormone axes of the classical steroid (ecdysone) and methyl epoxy sesquiterpenoid (juvenile hormone)

Last Modified: 4/16/2014
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