An rxr/usp homolog from the parasitic nematode, Dirofilaria immitis.
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 Dirofilaria immitis, the causative agent of dog heartworm disease. In D. immitis, molting from the third to the fourth larval stage can be induced in vitro by the insect molting hormone, 20-hydroxyecdysone, suggesting that this, or some related steroid, may play a similar role in the development of D. immitis. The holoreceptor of 20-hydroxyecdysone consists of two nuclear receptors (NRs) ecdysone receptor (EcR) and ultraspiracle (USP), USP being the insect orthologue of the vertebrate RXR. We have identified a D. immitis rxr/usp, Di-rxr-1 (NR2B4). Di-RXR-1 can bind in vitro to EcR and DHR38, both known insect USP partners. Like, USP, it activates transcription in Drosophila Schneider S2 cells in a 20-hydroxyecdysone-dependent manner, via its interaction with the endogenous EcR protein. By Northern blot analysis, Di-rxr-1 mRNA is detected in adult females, but not in males. This is the first characterization of a nematode rxr/usp.
Shea
Cathy
C
New England Biolabs, 32 Tozer Road, Beverly, MA 01915, USA.
Hough
David
D
Xiao
Jianping
J
Tzertzinis
George
G
Maina
Claude V
CV
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D018509:DNA, Helminth / Q000737:chemistry / Q000235:genetics; D004183:Dirofilaria immitis / Q000235:genetics* / Q000254:growth & development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D010802:Phylogeny; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D047488:Retinoid X Receptors; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation
D018076:DNA, Complementary; D018509:DNA, Helminth; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors