Transporter-mediated ecdysteroid trafficking across cell membranes: A novel target for insect growth regulators

Abstract

Ecdysteroids are a class of steroid hormones in arthropods that control molting and metamorphosis through interaction with intracellular nuclear receptors. In contrast to the extensive literature describing their biosynthetic pathways and signaling components, little has been known about how these hormones are traveling into and out of the cells through lipid bilayers of the cell membranes. Recently, a series of studies conducted in the fruit fly Drosophila melanogaster revealed that membrane transporters have critical functions in trafficking ecdysteroids across cell membranes, challenging the classical simple diffusion model of steroid hormone transport. Here we summarize recent advances in our understanding of membrane transporters involved in ecdysteroid signaling in Drosophila, with particular focus on Ecdysone Importer (EcI) that is involved in ecdysteroid uptake in peripheral tissues. We then discuss the potential advantage of EcI blockers as a novel pest management tool as compared to classical insect growth regulators.

Keywords: EcR; Ecdysone Importer; IGR; ecdysone; ecdysteroid.

Fig. 1. Schematic diagram of ecdysone release from Drosophila PG cells. After its biosynthesis, ecdysone is incorporated into secretory vesicles by an ABC transporter called Atet (pink) and released into the hemolymph through exocytosis.

Fig. 2. Differential cellular entry mechanisms for 20E and CF. 20E is incorporated into its target cells through EcI (dark blue), whereas CF enters the cells through a distinct, unknown mechanism (brown). These agonists bind to EcR (pink) and induce gene expression.

Fig. 3. Comparison of the modes-of-action of known ecdysone agonists and EcI blockers. 20E enters its target cells through EcI (dark blue) and binds to EcR (pink) to induce gene expression. Known ecdysone agonists also enter the cells to interact with EcR and disrupt ecdysteroid signaling (A), but this makes them susceptible to intracellular insecticide resistance machineries such as multidrug ABC transporters that pump out pesticides out of the cells (purple in B), or detoxification enzymes that break them down (green in C). In contrast, EcI blockers are expected to circumvent such resistance machinery as they can interact with EcI from extracellular space (D).