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1.
Proc Natl Acad Sci U S A ; 111(11): 4025-30, 2014 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-24550463

RESUMO

Genome sequences predict the presence of many 2-oxoglutarate (2OG)-dependent oxygenases of unknown biochemical and biological functions in Drosophila. Ribosomal protein hydroxylation is emerging as an important 2OG oxygenase catalyzed pathway, but its biological functions are unclear. We report investigations on the function of Sudestada1 (Sud1), a Drosophila ribosomal oxygenase. As with its human and yeast homologs, OGFOD1 and Tpa1p, respectively, we identified Sud1 to catalyze prolyl-hydroxylation of the small ribosomal subunit protein RPS23. Like OGFOD1, Sud1 catalyzes a single prolyl-hydroxylation of RPS23 in contrast to yeast Tpa1p, where Pro-64 dihydroxylation is observed. RNAi-mediated Sud1 knockdown hinders normal growth in different Drosophila tissues. Growth impairment originates from both reduction of cell size and diminution of the number of cells and correlates with impaired translation efficiency and activation of the unfolded protein response in the endoplasmic reticulum. This is accompanied by phosphorylation of eIF2α and concomitant formation of stress granules, as well as promotion of autophagy and apoptosis. These observations, together with those on enzyme homologs described in the companion articles, reveal conserved biochemical and biological roles for a widely distributed ribosomal oxygenase.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/enzimologia , Homeostase/fisiologia , Prolil Hidroxilases/metabolismo , Biossíntese de Proteínas/fisiologia , Proteínas Ribossômicas/metabolismo , Animais , Animais Geneticamente Modificados , Apoptose/genética , Autofagia/genética , Western Blotting , Pesos e Medidas Corporais , Cromatografia Líquida , Primers do DNA/genética , Proteínas de Drosophila/genética , Corpo Adiposo/citologia , Feminino , Técnicas de Silenciamento de Genes , Hidroxilação , Prolil Hidroxilases/genética , Processamento de Proteína Pós-Traducional/fisiologia , Interferência de RNA , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Ribossômicas/genética , Espectrometria de Massas em Tandem , Resposta a Proteínas não Dobradas/genética
2.
Curr Biol ; 33(22): 4771-4785.e7, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37804828

RESUMO

Olfaction is a fundamental sense guiding animals to their food. How the olfactory system evolves and influences behavior is still poorly understood. Here, we selected five drosophilid species, including Drosophila melanogaster, inhabiting different ecological niches to compare their olfactory systems at multiple levels. We first identified ecologically relevant natural food odorants from every species and established species-specific odorant preferences. To compare odor coding in sensory neurons, we analyzed the antennal lobe (AL) structure, generated glomerular atlases, and developed GCaMP transgenic lines for all species. Although subsets of glomeruli showed distinct tuning profiles, odorants inducing species-specific preferences were coded generally similarly. Species distantly related or occupying different habitats showed more evident differences in odor coding, and further analysis revealed that changes in olfactory receptor (OR) sequences partially explain these differences. Our results demonstrate that genetic distance in phylogeny and ecological niche occupancy are key determinants in the evolution of ORs, AL structures, odor coding, and behavior. Interestingly, changes in odor coding among species could not be explained by evolutionary changes at a single olfactory processing level but rather are a complex phenomenon based on changes at multiple levels.


Assuntos
Odorantes , Neurônios Receptores Olfatórios , Animais , Drosophila/genética , Drosophila melanogaster/genética , Neurônios Receptores Olfatórios/fisiologia , Olfato/fisiologia , Condutos Olfatórios/fisiologia
3.
Cell Rep ; 24(12): 3156-3166.e4, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30231999

RESUMO

In Drosophila, ecdysone hormone levels determine the timing of larval development. Its production is regulated by the stereotypical rise in prothoracicotropic hormone (PTTH) levels. Additionally, ecdysone levels can also be modulated by nutrition (specifically by amino acids) through their action on Drosophila insulin-like peptides (Dilps). Moreover, in glia, amino-acid-sensitive production of Dilps regulates brain development. In this work, we describe the function of an SLC7 amino acid transporter, Sobremesa (Sbm). Larvae with reduced Sbm levels in glia remain in third instar for an additional 24 hr. These larvae show reduced brain growth with increased body size but do not show reduction in insulin signaling or production. Interestingly, Sbm downregulation in glia leads to reduced Ecdysone production and a surprising delay in the rise of PTTH levels. Our work highlights Sbm as a modulator of both brain development and the timing of larval development via an amino-acid-sensitive and Dilp-independent function of glia.


Assuntos
Sistemas de Transporte de Aminoácidos/metabolismo , Encéfalo/crescimento & desenvolvimento , Drosophila melanogaster/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Neuroglia/metabolismo , Sistemas de Transporte de Aminoácidos/genética , Animais , Encéfalo/metabolismo , Drosophila melanogaster/metabolismo , Ecdisona/metabolismo , Hormônios de Inseto/metabolismo , Insulina/metabolismo
4.
Sci Rep ; 7(1): 14230, 2017 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-29079812

RESUMO

Microorganisms inhabiting fermenting fruit produce chemicals that elicit strong behavioral responses in flies. Depending on their ecological niche, individuals confer a positive or a negative valence to a chemical and, accordingly, they trigger either attractive or repulsive behaviors. We studied the case of bacterial short-chain fatty acids (SCFA) that trigger opposite behaviors in adult and larvae of Drosophila melanogaster. We determined that SCFA-attractive responses depend on two larval exclusive chemoreceptors, Or30a and Or94b. Of those SCFA, propionic acid improves larval survival in suboptimal rearing conditions and supports growth. Olfactory detection of propionic acid specifically is sufficient to trigger feeding behaviors, and this effect requires the correct activity of Or30a+ and Or94b+ olfactory sensory neurons. Additionally, we studied the case of the invasive pest Drosophila suzukii that lives on undamaged ripe fruit with less SCFA production. Contrary to D. melanogaster, D. suzukii larvae show reduced attraction towards propionic acid, which does not trigger feeding behavior in this invasive species. Our results demonstrate the relevance of propionic acid as an orexigenic signal in D. melanogaster larvae. Moreover, this study underlines that the changes on ecological niche are accompanied with alterations of olfactory preferences and vital olfactory driven behaviors.


Assuntos
Apetite/efeitos dos fármacos , Bactérias/metabolismo , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/fisiologia , Ácidos Graxos Voláteis/farmacologia , Larva/efeitos dos fármacos , Olfato/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Ácidos Graxos Voláteis/biossíntese , Comportamento Alimentar/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/fisiologia , Propionatos/farmacologia , Análise de Sobrevida
5.
Mol Biol Cell ; 25(6): 916-24, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24430872

RESUMO

Mammalian insulin-degrading enzyme (IDE) cleaves insulin, among other peptidic substrates, but its function in insulin signaling is elusive. We use the Drosophila system to define the function of IDE in the regulation of growth and metabolism. We find that either loss or gain of function of Drosophila IDE (dIDE) can restrict growth in a cell-autonomous manner by affecting both cell size and cell number. dIDE can modulate Drosophila insulin-like peptide 2 levels, thereby restricting activation of the phosphatidylinositol-3-phosphate kinase pathway and promoting activation of Drosophila forkhead box, subgroup O transcription factor. Larvae reared in high sucrose exhibit delayed developmental timing due to insulin resistance. We find that dIDE loss of function exacerbates this phenotype and that mutants display increased levels of circulating sugar, along with augmented expression of a lipid biosynthesis marker. We propose that dIDE is a modulator of insulin signaling and that its loss of function favors insulin resistance, a hallmark of diabetes mellitus type II.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Insulisina/genética , Transdução de Sinais , Animais , Tamanho Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Insulisina/metabolismo , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Neuropeptídeos , Fenótipo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Asas de Animais/citologia , Asas de Animais/metabolismo
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