Altered expression of CG5961, a putative Drosophila melanogaster homologue of FBXO9, provides a new model of Parkinson disease.
Identifieur interne : 000231 ( PubMed/Curation ); précédent : 000230; suivant : 000232Altered expression of CG5961, a putative Drosophila melanogaster homologue of FBXO9, provides a new model of Parkinson disease.
Auteurs : E M Merzetti [Canada] ; B E Staveley [Canada]Source :
- Genetics and molecular research : GMR [ 1676-5680 ] ; 2016.
English descriptors
- KwdEn :
- Animals, Animals, Genetically Modified, Base Sequence, Conserved Sequence, Dopaminergic Neurons (metabolism), Drosophila Proteins (biosynthesis), Drosophila Proteins (genetics), Drosophila Proteins (metabolism), Drosophila melanogaster, F-Box Proteins (biosynthesis), F-Box Proteins (genetics), F-Box Proteins (metabolism), Female, Humans, Male, Models, Animal, Parkinson Disease (genetics), Parkinson Disease (metabolism), Signal Transduction, Ubiquitin, Ubiquitin-Protein Ligases (metabolism).
- MESH :
- chemical , biosynthesis : Drosophila Proteins, F-Box Proteins.
- chemical , genetics : Drosophila Proteins, F-Box Proteins.
- genetics : Parkinson Disease.
- metabolism : Dopaminergic Neurons, Drosophila Proteins, F-Box Proteins, Parkinson Disease, Ubiquitin-Protein Ligases.
- Animals, Animals, Genetically Modified, Base Sequence, Conserved Sequence, Drosophila melanogaster, Female, Humans, Male, Models, Animal, Signal Transduction, Ubiquitin.
Abstract
F-box proteins act as the protein recognition component of the Skp-Cul-F-box class of ubiquitin ligases. Two members of a gene sub-family encoding these proteins, FBXO7 and FBXO32, have been implicated in the onset and progression of degenerative disease. FBXO7 is responsible for rare genetic forms of Parkinson disease, while FBXO32 has been implicated in muscle wasting. The third gene in this family, FBXO9, is related to growth signaling, but the role of this gene in degenerative disease pathways has not been thoroughly investigated. Characterizing the putative Drosophila melanogaster homologue of this gene, CG5961, enables modeling and analysis of the consequence of targeted alteration of gene function and the effects on the overall health of the organism. Comparison of the protein domains of Homo sapiens FBXO9 and the putative D. melanogaster homologue CG5961 revealed a high degree of conservation between the protein domains. Directed expression of CG5961 (via CG5961(EP)) and inhibition of CG5961 (through a stable RNAi transgene) in the developing D. melanogaster eye caused abnormalities in adult structures (ommatidia and inter-ommatidial bristles). Directed expression of either CG5961 or CG5961-RNAi in the dopaminergic neurons led to a reduced lifespan compared to that in lacZ controls. We showed that protein structures of CG5961 and FBXO9 are highly similar and studied the effects of altered expression of CG5961 in neuron-rich tissues. Our results suggest that CG5961 activity is necessary for the proper formation of neuronal tissue and that targeted alteration of gene expression in dopaminergic neurons leads to a reduced lifespan.
DOI: 10.4238/gmr.15028579
PubMed: 27173356
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last="Merzetti">E M Merzetti</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology, Memorial University of Newfoundland, Newfoundland and Labrador, A1B 3X9, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, Memorial University of Newfoundland, Newfoundland and Labrador, A1B 3X9</wicri:regionArea></affiliation></author><author><name sortKey="Staveley, B E" sort="Staveley, B E" uniqKey="Staveley B" first="B E" last="Staveley">B E Staveley</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology, Memorial University of Newfoundland, Newfoundland and Labrador, A1B 3X9, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, Memorial University of Newfoundland, Newfoundland and Labrador, A1B 3X9</wicri:regionArea></affiliation></author></analytic><series><title level="j">Genetics and molecular research : GMR</title><idno 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xml:lang="en">F-box proteins act as the protein recognition component of the Skp-Cul-F-box class of ubiquitin ligases. Two members of a gene sub-family encoding these proteins, FBXO7 and FBXO32, have been implicated in the onset and progression of degenerative disease. FBXO7 is responsible for rare genetic forms of Parkinson disease, while FBXO32 has been implicated in muscle wasting. The third gene in this family, FBXO9, is related to growth signaling, but the role of this gene in degenerative disease pathways has not been thoroughly investigated. Characterizing the putative Drosophila melanogaster homologue of this gene, CG5961, enables modeling and analysis of the consequence of targeted alteration of gene function and the effects on the overall health of the organism. Comparison of the protein domains of Homo sapiens FBXO9 and the putative D. melanogaster homologue CG5961 revealed a high degree of conservation between the protein domains. Directed expression of CG5961 (via CG5961(EP)) and inhibition of CG5961 (through a stable RNAi transgene) in the developing D. melanogaster eye caused abnormalities in adult structures (ommatidia and inter-ommatidial bristles). Directed expression of either CG5961 or CG5961-RNAi in the dopaminergic neurons led to a reduced lifespan compared to that in lacZ controls. We showed that protein structures of CG5961 and FBXO9 are highly similar and studied the effects of altered expression of CG5961 in neuron-rich tissues. Our results suggest that CG5961 activity is necessary for the proper formation of neuronal tissue and that targeted alteration of gene expression in dopaminergic neurons leads to a reduced lifespan.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27173356</PMID><DateCreated><Year>2016</Year><Month>05</Month><Day>13</Day></DateCreated><DateCompleted><Year>2017</Year><Month>03</Month><Day>16</Day></DateCompleted><DateRevised><Year>2017</Year><Month>03</Month><Day>16</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1676-5680</ISSN><JournalIssue CitedMedium="Internet"><Volume>15</Volume><Issue>2</Issue><PubDate><Year>2016</Year><Month>May</Month><Day>09</Day></PubDate></JournalIssue><Title>Genetics and molecular research : GMR</Title><ISOAbbreviation>Genet. Mol. 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Characterizing the putative Drosophila melanogaster homologue of this gene, CG5961, enables modeling and analysis of the consequence of targeted alteration of gene function and the effects on the overall health of the organism. Comparison of the protein domains of Homo sapiens FBXO9 and the putative D. melanogaster homologue CG5961 revealed a high degree of conservation between the protein domains. Directed expression of CG5961 (via CG5961(EP)) and inhibition of CG5961 (through a stable RNAi transgene) in the developing D. melanogaster eye caused abnormalities in adult structures (ommatidia and inter-ommatidial bristles). Directed expression of either CG5961 or CG5961-RNAi in the dopaminergic neurons led to a reduced lifespan compared to that in lacZ controls. We showed that protein structures of CG5961 and FBXO9 are highly similar and studied the effects of altered expression of CG5961 in neuron-rich tissues. 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