Molecular evidence for a functional ecdysone signaling system in Brugia malayi.
BACKGROUND:Filarial nematodes, including Brugia malayi, the causative agent of lymphatic filariasis, undergo molting in both arthropod and mammalian hosts to complete their life cycles. An understanding of how these parasites cross developmental checkpoints may reveal potential targets for intervent...
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ftdoajarticles:oai:doaj.org/article:11003ea932654e8a89353b05cd571b1d 2023-05-15T15:16:30+02:00 Molecular evidence for a functional ecdysone signaling system in Brugia malayi. George Tzertzinis Ana L Egaña Subba Reddy Palli Marc Robinson-Rechavi Chris R Gissendanner Canhui Liu Thomas R Unnasch Claude V Maina 2010-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000625 https://doaj.org/article/11003ea932654e8a89353b05cd571b1d EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2834746?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000625 https://doaj.org/article/11003ea932654e8a89353b05cd571b1d PLoS Neglected Tropical Diseases, Vol 4, Iss 3, p e625 (2010) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2010 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000625 2022-12-31T14:15:41Z BACKGROUND:Filarial nematodes, including Brugia malayi, the causative agent of lymphatic filariasis, undergo molting in both arthropod and mammalian hosts to complete their life cycles. An understanding of how these parasites cross developmental checkpoints may reveal potential targets for intervention. Pharmacological evidence suggests that ecdysteroids play a role in parasitic nematode molting and fertility although their specific function remains unknown. In insects, ecdysone triggers molting through the activation of the ecdysone receptor: a heterodimer of EcR (ecdysone receptor) and USP (Ultraspiracle). METHODS AND FINDINGS:We report the cloning and characterization of a B. malayi EcR homologue (Bma-EcR). Bma-EcR dimerizes with insect and nematode USP/RXRs and binds to DNA encoding a canonical ecdysone response element (EcRE). In support of the existence of an active ecdysone receptor in Brugia we also cloned a Brugia rxr (retinoid X receptor) homolog (Bma-RXR) and demonstrate that Bma-EcR and Bma-RXR interact to form an active heterodimer using a mammalian two-hybrid activation assay. The Bma-EcR ligand-binding domain (LBD) exhibits ligand-dependent transactivation via a GAL4 fusion protein combined with a chimeric RXR in mammalian cells treated with Ponasterone-A or a synthetic ecdysone agonist. Furthermore, we demonstrate specific up-regulation of reporter gene activity in transgenic B. malayi embryos transfected with a luciferase construct controlled by an EcRE engineered in a B. malayi promoter, in the presence of 20-hydroxy-ecdysone. CONCLUSIONS:Our study identifies and characterizes the two components (Bma-EcR and Bma-RXR) necessary for constituting a functional ecdysteroid receptor in B. malayi. Importantly, the ligand binding domain of BmaEcR is shown to be capable of responding to ecdysteroid ligands, and conversely, ecdysteroids can activate transcription of genes downstream of an EcRE in live B. malayi embryos. These results together confirm that an ecdysone signaling system operates in B. ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 4 3 e625 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 George Tzertzinis Ana L Egaña Subba Reddy Palli Marc Robinson-Rechavi Chris R Gissendanner Canhui Liu Thomas R Unnasch Claude V Maina Molecular evidence for a functional ecdysone signaling system in Brugia malayi. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Filarial nematodes, including Brugia malayi, the causative agent of lymphatic filariasis, undergo molting in both arthropod and mammalian hosts to complete their life cycles. An understanding of how these parasites cross developmental checkpoints may reveal potential targets for intervention. Pharmacological evidence suggests that ecdysteroids play a role in parasitic nematode molting and fertility although their specific function remains unknown. In insects, ecdysone triggers molting through the activation of the ecdysone receptor: a heterodimer of EcR (ecdysone receptor) and USP (Ultraspiracle). METHODS AND FINDINGS:We report the cloning and characterization of a B. malayi EcR homologue (Bma-EcR). Bma-EcR dimerizes with insect and nematode USP/RXRs and binds to DNA encoding a canonical ecdysone response element (EcRE). In support of the existence of an active ecdysone receptor in Brugia we also cloned a Brugia rxr (retinoid X receptor) homolog (Bma-RXR) and demonstrate that Bma-EcR and Bma-RXR interact to form an active heterodimer using a mammalian two-hybrid activation assay. The Bma-EcR ligand-binding domain (LBD) exhibits ligand-dependent transactivation via a GAL4 fusion protein combined with a chimeric RXR in mammalian cells treated with Ponasterone-A or a synthetic ecdysone agonist. Furthermore, we demonstrate specific up-regulation of reporter gene activity in transgenic B. malayi embryos transfected with a luciferase construct controlled by an EcRE engineered in a B. malayi promoter, in the presence of 20-hydroxy-ecdysone. CONCLUSIONS:Our study identifies and characterizes the two components (Bma-EcR and Bma-RXR) necessary for constituting a functional ecdysteroid receptor in B. malayi. Importantly, the ligand binding domain of BmaEcR is shown to be capable of responding to ecdysteroid ligands, and conversely, ecdysteroids can activate transcription of genes downstream of an EcRE in live B. malayi embryos. These results together confirm that an ecdysone signaling system operates in B. ... |
format |
Article in Journal/Newspaper |
author |
George Tzertzinis Ana L Egaña Subba Reddy Palli Marc Robinson-Rechavi Chris R Gissendanner Canhui Liu Thomas R Unnasch Claude V Maina |
author_facet |
George Tzertzinis Ana L Egaña Subba Reddy Palli Marc Robinson-Rechavi Chris R Gissendanner Canhui Liu Thomas R Unnasch Claude V Maina |
author_sort |
George Tzertzinis |
title |
Molecular evidence for a functional ecdysone signaling system in Brugia malayi. |
title_short |
Molecular evidence for a functional ecdysone signaling system in Brugia malayi. |
title_full |
Molecular evidence for a functional ecdysone signaling system in Brugia malayi. |
title_fullStr |
Molecular evidence for a functional ecdysone signaling system in Brugia malayi. |
title_full_unstemmed |
Molecular evidence for a functional ecdysone signaling system in Brugia malayi. |
title_sort |
molecular evidence for a functional ecdysone signaling system in brugia malayi. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doi.org/10.1371/journal.pntd.0000625 https://doaj.org/article/11003ea932654e8a89353b05cd571b1d |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 4, Iss 3, p e625 (2010) |
op_relation |
http://europepmc.org/articles/PMC2834746?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000625 https://doaj.org/article/11003ea932654e8a89353b05cd571b1d |
op_doi |
https://doi.org/10.1371/journal.pntd.0000625 |
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PLoS Neglected Tropical Diseases |
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4 |
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3 |
container_start_page |
e625 |
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1766346793558212608 |