Genetic evidence for function of the bhlh-pas protein gce/met as a juvenile hormone receptor
| Autor: | Jean-Philippe Charles, Ronald J. Hill, Marek Jindra, Vlastimil Smykal, Mirka Uhlirova |
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| Přispěvatelé: | Czech Academy of Sciences [Prague] ( ASCR ), CSIRO, Commonwealth Scientific and Industrial Research Organisation, North Ryde, New South Wales, Australie, University of Cologne, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), University of South Bohemia, Commonwealth Scientific and Industrial Research Organisation, Jindra, Marek, Hill, Ronald J., Czech Academy of Sciences [Prague] (ASCR), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Czech Academy of Sciences [Prague] (CAS), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
lcsh:QH426-470 Transgene Cell Line Animals Genetically Modified Genetics Melanogaster Basic Helix-Loop-Helix Transcription Factors Animals Drosophila Proteins [ SDV.BDD ] Life Sciences [q-bio]/Development Biology Receptor Molecular Biology Transcription factor [SDV.BDD]Life Sciences [q-bio]/Development Biology Genetics (clinical) Ecology Evolution Behavior and Systematics Regulation of gene expression biology fungi Biologie du développement Gene Expression Regulation Developmental biology.organism_classification Development Biology Cell biology Juvenile Hormones lcsh:Genetics Drosophila melanogaster Juvenile hormone Fatty Acids Unsaturated Drosophila Protein Protein Binding Signal Transduction Transcription Factors Research Article |
| Zdroj: | PLoS Genetics PLoS Genetics, Public Library of Science, 2015, 11 (7), pp.1-16. 〈10.1371/journal.pgen.1005394〉 Plos Genetics 7 (11), 1-16. (2015) PLoS Genetics, Public Library of Science, 2015, 11 (7), pp.1-16. ⟨10.1371/journal.pgen.1005394⟩ PLoS Genetics, Vol 11, Iss 7, p e1005394 (2015) |
| ISSN: | 1553-7390 1553-7404 |
| DOI: | 10.1371/journal.pgen.1005394〉 |
| Popis: | Juvenile hormones (JHs) play a major role in controlling development and reproduction in insects and other arthropods. Synthetic JH-mimicking compounds such as methoprene are employed as potent insecticides against significant agricultural, household and disease vector pests. However, a receptor mediating effects of JH and its insecticidal mimics has long been the subject of controversy. The bHLH-PAS protein Methoprene-tolerant (Met), along with its Drosophila melanogaster paralog germ cell-expressed (Gce), has emerged as a prime JH receptor candidate, but critical evidence that this protein must bind JH to fulfill its role in normal insect development has been missing. Here, we show that Gce binds a native D. melanogaster JH, its precursor methyl farnesoate, and some synthetic JH mimics. Conditional on this ligand binding, Gce mediates JH-dependent gene expression and the hormone's vital role during development of the fly. Any one of three different single amino acid mutations in the ligand-binding pocket that prevent binding of JH to the protein block these functions. Only transgenic Gce capable of binding JH can restore sensitivity to JH mimics in D. melanogaster Met-null mutants and rescue viability in flies lacking both Gce and Met that would otherwise die at pupation. Similarly, the absence of Gce and Met can be compensated by expression of wild-type but not mutated transgenic D. melanogaster Met protein. This genetic evidence definitively establishes Gce/Met in a JH receptor role, thus resolving a long-standing question in arthropod biology. Author Summary Juvenile hormones (JHs) play critical roles in the development of arthropods, comprising half the animal biomass of the oceans and over a million insect species, which have an enormous impact on ecosystems, agriculture (pollinators and pests) and health of mankind (disease vectors). Despite decades of research, a receptor for these unique sesquiterpenoid hormones has remained elusive. Here, we provide definitive genetic evidence establishing that the essential biological function of the Gce/Met protein during insect development is critically dependent on its ability to bind JH, in effect functionally defining a JH receptor. Unequivocal identification of a JH receptor has profound implications for our understanding of arthropod biology. It also defines a molecular target for development of environmentally friendly, safer insecticides. |
| Databáze: | OpenAIRE |
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