title: Dirofilaria immitis encodes Di-nhr-7, a putative orthologue of the Drosophila ecdysone-regulated E78 gene.
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 elucidate the general mechanisms of these illnesses and suggest potential targets for intervention. A useful model system for the study of human filariasis is the 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 hormone 20-OH ecdysone, suggesting that ecdysone, or some related hormone, may play a similar role in the development of D. immitis. Ecdysone has a well-characterized developmental role in insects, where it is involved in the control of molting and metamorphosis. We have identified a D. immitis orthologue of the Drosophila ecdysone response early gene E78, a member of the nuclear receptor (NR) superfamily. The D. immitis gene, Di-nhr-7 (NR1E1) encodes at least three isoforms, including two potential negative regulatory isoforms, and is expressed in a sex-specific manner. An MBP/Di-NHR-7 fusion protein is able to bind to DNA response elements that are recognized by the closely related mammalian NR Rev-erb(alpha).
authors.affiliation: New England Biolabs, Inc., Beverly, MA 01915, USA. kcrossgrove@loyola.edu
authors.forename: Kirsten
authors.initials: K
authors.lastname: Crossgrove
authors.forename: Vincent
authors.initials: V
authors.lastname: Laudet
authors.forename: Claude V
authors.initials: CV
authors.lastname: Maina
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D004183:Dirofilaria immitis / Q000235:genetics*; D004184:Dirofilariasis / Q000469:parasitology; D004330:Drosophila / Q000737:chemistry / Q000235:genetics*; D029721:Drosophila Proteins; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015801:Helminth Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D018978:Molting / Q000235:genetics; D009866:Oogenesis / Q000235:genetics; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011988:Receptors, Thyroid Hormone; D020218:Response Elements / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012727:Sex Characteristics
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C083810:Eip78C protein, drosophila; D015801:Helminth Proteins; C451424:NHR-7 protein, Dirofilaria immitis; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011988:Receptors, Thyroid Hormone