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1.
Cell Death Differ ; 15(6): 1009-18, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18309327

RESUMEN

Apoptosis-inducing factor (AIF) is a phylogenetically conserved redox-active flavoprotein that contributes to cell death and oxidative phosphorylation in Saccharomyces cerevisiae, Caenorhabditis elegans, mouse and humans. AIF has been characterized as a caspase-independent death effector that is activated by its translocation from mitochondria to the cytosol and nucleus. Here, we report the molecular characterization of AIF in Drosophila melanogaster, a species in which most cell deaths occur in a caspase-dependent manner. Interestingly, knockout of zygotic D. melanogaster AIF (DmAIF) expression using gene targeting resulted in decreased embryonic cell death and the persistence of differentiated neuronal cells at late embryonic stages. Although knockout embryos hatch, they undergo growth arrest at early larval stages, accompanied by mitochondrial respiratory dysfunction. Transgenic expression of DmAIF misdirected to the extramitochondrial compartment (DeltaN-DmAIF), but not wild-type DmAIF, triggered ectopic caspase activation and cell death. DeltaN-DmAIF-induced death was not blocked by removal of caspase activator Dark or transgenic expression of baculoviral caspase inhibitor p35, but was partially inhibited by Diap1 overexpression. Knockdown studies revealed that DeltaN-DmAIF interacts genetically with the redox protein thioredoxin-2. In conclusion, we show that Drosophila AIF is a mitochondrial effector of cell death that plays roles in developmentally regulated cell death and normal mitochondrial function.


Asunto(s)
Factor Inductor de la Apoptosis/fisiología , Apoptosis , Proteínas de Drosophila/fisiología , Drosophila melanogaster/embriología , Secuencia de Aminoácidos , Animales , Factor Inductor de la Apoptosis/química , Factor Inductor de la Apoptosis/genética , Sistema Nervioso Central/embriología , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Drosophila melanogaster/anatomía & histología , Drosophila melanogaster/metabolismo , Metabolismo Energético , Ojo/anatomía & histología , Proteínas Mitocondriales/química , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/fisiología , Datos de Secuencia Molecular , Mutación , Homología de Secuencia de Aminoácido , Tiorredoxinas/metabolismo
2.
Genetics ; 159(3): 1059-72, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11729153

RESUMEN

We identified a large family of putative odorant-binding protein (OBP) genes in the genome of Drosophila melanogaster. Some of these genes are present in large clusters in the genome. Most members are expressed in various taste organs, including gustatory sensilla in the labellum, the pharyngeal labral sense organ, dorsal and ventral cibarial organs, as well as taste bristles located on the wings and tarsi. Some of the gustatory OBPs are expressed exclusively in taste organs, but most are expressed in both olfactory and gustatory sensilla. Multiple binding proteins can be coexpressed in the same gustatory sensillum. Cells in the tarsi that express OBPs are required for normal chemosensation mediated through the leg, as ablation of these cells dramatically reduces the sensitivity of the proboscis extension reflex to sucrose. Finally, we show that OBP genes expressed in the pharyngeal taste sensilla are still expressed in the poxneuro genetic background while OBPs expressed in the labellum are not. These findings support a broad role for members of the OBP family in gustation and olfaction and suggest that poxneuro is required for cell fate determination of labellar but not pharyngeal taste organs.


Asunto(s)
Proteínas de Drosophila , Drosophila melanogaster/genética , Drosophila melanogaster/fisiología , Proteínas de la Membrana/metabolismo , Bulbo Olfatorio/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores Odorantes/biosíntesis , Receptores Odorantes/genética , Secuencia de Aminoácidos , Animales , Animales Modificados Genéticamente , Linaje de la Célula , Relación Dosis-Respuesta a Droga , Genoma , Operón Lac , Datos de Secuencia Molecular , Mutación , Bulbo Olfatorio/embriología , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Olfato , Sacarosa/farmacología , Gusto , Factores de Tiempo , Distribución Tisular , beta-Galactosidasa/metabolismo
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