An EcR homolog from the filarial parasite, Dirofilaria immitis requires a ligand-activated partner for transactivation

Abstract

Filarial parasites are responsible for several serious human diseases with symptoms such as lymphoedema, elephantiasis, and blindness. An understanding of how these parasites pass through developmental checkpoints may suggest potential targets for intervention. A useful model system for the study of the human parasites is the closely related nematode, D. immitis, the causative agent of dog heartworm disease. Ecdysteroids have been identified in filarial nematodes and have been shown to have a biological affect both on molting and microfilarial production. The ecdysteroid, 20-hydroxyecdysone and its receptor, EcR, have a well-characterized developmental role in insects, where it is involved in the control of molting and metamorphosis. We have identified a D. immitis nuclear receptor, DiEcR that shows strong sequence similarity to the insect EcR and shares many of its biochemical properties, including ligand-dependent activation of transcription. However, unlike most insect EcRs, DiEcR requires a ligand-activated RXR partner to exhibit ligand-dependent transcriptional activation of a reporter gene in tissue culture.