Asunto(s)
Apoptosis/fisiología , Proteínas de Drosophila , Drosophila melanogaster/fisiología , Fagocitosis/fisiología , Naranja de Acridina/metabolismo , Animales , Bioensayo/métodos , Antígenos CD36/metabolismo , Línea Celular , Drosophila melanogaster/embriología , Proteínas ELAV , Estructuras Embrionarias/fisiología , Estructuras Embrionarias/ultraestructura , Proteínas de la Matriz Extracelular/metabolismo , Colorantes Fluorescentes/metabolismo , Técnicas de Preparación Histocitológica , Etiquetado Corte-Fin in Situ , Macrófagos/metabolismo , Microscopía Fluorescente , Péptidos/metabolismo , Peroxidasa/metabolismo , Receptores Inmunológicos/metabolismo , Receptores Depuradores , Ribonucleoproteínas/metabolismo , Transfección , beta-Galactosidasa/metabolismo , PeroxidasinaRESUMEN
The Drosophila epidermal growth factor receptor (EGFR), functioning through the Ras/Raf/MAPK pathway, promotes cell proliferation and differentiation. Recent work has demonstrated that EGFR functions via the same Ras/Raf/MAPK pathway to promote cell survival. This review summarizes the role of EGFR in differentiation and survival during Drosophila eye development.
RESUMEN
Activation of Ras inhibits apoptosis during Drosophila development. Genetic evidence indicates that Ras antiapoptotic activity in the developing eye is regulated by the Drosophila EGF receptor and operates through the Raf/MAPK pathway. Decreased activity of this pathway enhances, and increased activity suppresses, apoptosis induced by ectopic expression of the cell death regulators reaper (rpr) and head involution defective (hid). In addition, ectopic activation of the Ras/MAPK pathway in the developing embryo and in the developing eye suppresses naturally occurring apoptosis and regulates the transcription of the proapoptotic gene hid. Null alleles of hid recapitulate the antiapoptotic activities of Ras/MAPK, providing genetic evidence that downregulation of hid is an important mechanism by which Ras promotes survival.
Asunto(s)
Apoptosis/fisiología , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Supervivencia Celular , Proteínas de Drosophila , Quinasas MAP Reguladas por Señal Extracelular , Neuropéptidos/genética , Proteínas Quinasas , Proteínas ras/metabolismo , Alelos , Animales , Proteínas Quinasas Dependientes de Calcio-Calmodulina/genética , Proteínas de Unión al ADN , Regulación hacia Abajo , Drosophila melanogaster/citología , Drosophila melanogaster/embriología , Drosophila melanogaster/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Ojo/embriología , Ojo/metabolismo , Ojo/ultraestructura , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Regulación del Desarrollo de la Expresión Génica , Hibridación in Situ , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Modelos Biológicos , Mutación , Proteínas del Tejido Nervioso , Neuropéptidos/metabolismo , Péptidos/genética , Péptidos/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Receptores de Péptidos de Invertebrados/antagonistas & inhibidores , Receptores de Péptidos de Invertebrados/genética , Receptores de Péptidos de Invertebrados/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Transducción de Señal , Factores de Transcripción , Proteínas ras/genéticaRESUMEN
Rab6 is a GTP binding protein that regulates vesicular trafficking within the Golgi and post-Golgi compartments. We overexpressed wild-type, a GTPase defective (Q71L), and a guanine nucleotide binding defective (N125I) Rab6 protein in Drosophila photoreceptors to assess the in vivo role of Rab6 in the trafficking of rhodopsin and other proteins. Expression of Drab6(Q71L) greatly reduced the steady state levels of two rhodopsins, Rh1 and Rh3, whereas Drab6(wt) and Drab6(N125I) showed weaker effects. Analysis of a strain carrying Rh1 rhodopsin under a heat shock promoter showed that Drab6(Q71L), but not Drab6(wt) or Drab6(N125I), prevents the maturation of rhodopsin beyond an immature 40 kDa form. Drab6(Q71L) is a GTPase defective mutant, indicating that anterograde transport of rhodopsin requires Rab6 GTPase function. The three Drab6 strains had no effect on the expression of several other photoreceptor proteins. The Drab6(Q71L) photoreceptors show marked histological defects at young ages and degenerate over a two week time span. These results establish that rhodopsin is transported via a Rab6 regulated pathway and that defects in trafficking pathways lead to retinal degeneration.
Asunto(s)
Proteínas Portadoras/metabolismo , Proteínas de Drosophila , Drosophila/fisiología , Rodopsina/metabolismo , Proteínas de Unión al GTP rab , Proteínas ras/metabolismo , Animales , Transporte Biológico/fisiología , Proteínas Portadoras/genética , Electrofisiología , GTP Fosfohidrolasas/fisiología , Regulación de la Expresión Génica/genética , Aparato de Golgi/fisiología , Luz , Microscopía Electrónica , Mutación/genética , Células Fotorreceptoras de Invertebrados/fisiología , Células Fotorreceptoras de Invertebrados/ultraestructura , Regiones Promotoras Genéticas/genética , Retina/patología , Proteínas ras/genéticaRESUMEN
ninaE(D1), a dominant allele of the major Drosophila rhodopsin gene, expresses a rhodopsin that is predominantly recovered in a 80-kD complex that likely represents rhodopsin dimers. By driving either ninaE(D1) or ninaE+ expression from a heat-shock promoter, we show that the 80-kD rhodopsin complex forms immediately after gene activation. In wild type, but not ninaE(D1), rhodopsin monomeric forms are detected at later times. The generation of monomeric forms of wild-type rhodopsin is suppressed in vitamin A-deprived flies or in flies heterozygous for the dominant rhodopsin mutation. We also show that ninaE(D1) expression does not affect the maturation of another Drosophila visual pigment, Rh3. These results are consistent with the view that the ninaE(D1) rhodopsin antagonizes an early posttranslation process that is specific for maturation of the ninaE-encoded rhodopsin.
Asunto(s)
Proteínas de Drosophila , Drosophila melanogaster/genética , Proteínas del Ojo/genética , Expresión Génica , Células Fotorreceptoras de Invertebrados/metabolismo , Rodopsina/genética , Animales , Western Blotting , Proteínas HSP70 de Choque Térmico/genética , Reacción en Cadena de la Polimerasa , Rodopsina/metabolismo , Lugares Marcados de SecuenciaRESUMEN
Dominant mutations of the Drosophila ninaE-encoded rhodopsin are described that reduce the expression of wild-type rhodopsin and cause a slow, age-dependent form of retinal degeneration. A posttranslational event subsequent to the requirement for the ninaA-encoded cyclophilin is disrupted by the dominant mutations. Most of these dominant mutations are missense mutations that affect the physical properties of one of the seven transmembrane domains; another affects the cysteine involved in a disulfide linkage. The results indicate that misfolded or unstable mutant rhodopsin can interfere with maturation of wild-type rhodopsin, and that these cellular conditions may trigger retinal degeneration. In addition, these dominant rhodopsin mutations suppress the rapid degeneration seen in rdgC and norpA flies, indicating that high levels of rhodopsin are required.