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Regulação molecular da execução de mitose
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Abstract(s)
A regulação do ciclo celular e a integração de todos os sinais permite que as células mantenham a capacidade de se dividirem sem erros. A família de proteínas monopolar spindle (Mps) one binder (Mob) interagem com cinases que regulam o ciclo celular e a morfologia celular. A desregulação de membros da família Mob foi relacionado com o cancro. Esta família é altamente conservada desde levedura até aos seres humanos, contudo a função de alguns dos membros, como Mob1 e Mob3, durante o ciclo celular ainda não é totalmente conhecida. O objetivo deste projeto foi determinar a função dos genes Mob1 e Mob3 de Drosophila melanogaster no ciclo através da análise do fenótipo de mutantes.
Os mutantes nulos de Mob1 em Drosophila melanogaster (dMob1) apresentam figuras mitóticas alteradas em neuroblastos larvares de terceiro estadio. Nestas figuras foram observadas anomalias na focagem do fuso nos polos e na formação do fuso. Verificou-se a ocorrência de figuras com fusos mal formados apresentando uma torção do fuso, fusos mal definidos num dos polos, fusos com curvaturas acentuadas e fusos alongados que já deveriam ter iniciado a constrição para prosseguir para telófase.
Os mutantes nulos de Mob3 em Drosophila melanogaster (dMob3) são férteis e viáveis. Observou-se que os mutantes de dMob3 apresentaram regiões com manchas escuras que se assemelham manchas necróticas em várias regiões do corpo e, para além disso, apresentam também pequenas massas acinzentadas que se parecem com tumores. Estes mutantes dMob3 apresentam uma desorientação pronunciada. Durante a análise dos neuroblastos larvares, observou-se uma diminuição dos lóbulos óticos e defeitos mitóticos na focagem dos microtúbulos e no alinhamento dos cromossomas. Alguns indivíduos mutantes de dMob3 apresentam uma pelicula esbranquiçada sobre o corpo que se parece com fungos, sugerindo que poderão ter o sistema imune mais debilitado.
Em conclusão, os resultados obtidos sugerem que dMob1 poderá estar envolvido na dinâmica de microtúbulos e dMob3 poderá ser um novo gene supressor de tumores que poderá estar relacionado com vias de proliferação celular e vias que promovem a resposta imune.
The cell cycle regulation and integration of all signalling pathway allow the cells to maintain the ability to divide without errors. The monopolar spindle (Mps) one binder (Mob) protein family interacts with kinases that regulate the cell cycle and cell morphology. The dysregulation of Mob family members has been associated with cancer. This family is highly conserved from yeast to humans. However, the cell cycle function of some of its members, like Mob1 and Mob3, is still not known. The aim of this project is to determine the function of Drosophila melanogaster Mob1 and Mob3 genes during the cell cycle through mutant phenotype analysis. Mob1 null individuals in Drosophila melanogaster (dMob1) present altered mitotic figures in neuroblasts of Third stage instar larvae. Some of the observed anomalies were: unfocused spindle poles, malformed spindles (twisted-spindles or curved-spindles) and anaphases with elongated spindles which should have started the constriction of the membrane but are still not advancing to telophase. Mob3 null mutants in Drosophila melanogaster (dMob3) are fertile and viable indicating that this gene is not essential.. It was observed that dMob3 mutants present regions with darker pigmentation, similar to necrotic tissue in various regions of the body. They also present small grey masses resembling tumours. These dMob3 mutants show an accentuated disorientation on the climbing assay. During larval neuroblasts analysis, it was observed a decrease in the size of optical lobes. Mitotic defects were observed, namely the alignment of chromosomes and small defects in the mitotic fuse. Some dMob3 mutant individuals show a white membrane attached to the body which resembles fungi, suggesting the possibility of a weaker immune system. In conclusion, the results from this project suggest that dMob1 might be involved in regulating microtubule dynamics, and dMob3 might be a new tumour suppressor gene, possibly involved in immune response pathways
The cell cycle regulation and integration of all signalling pathway allow the cells to maintain the ability to divide without errors. The monopolar spindle (Mps) one binder (Mob) protein family interacts with kinases that regulate the cell cycle and cell morphology. The dysregulation of Mob family members has been associated with cancer. This family is highly conserved from yeast to humans. However, the cell cycle function of some of its members, like Mob1 and Mob3, is still not known. The aim of this project is to determine the function of Drosophila melanogaster Mob1 and Mob3 genes during the cell cycle through mutant phenotype analysis. Mob1 null individuals in Drosophila melanogaster (dMob1) present altered mitotic figures in neuroblasts of Third stage instar larvae. Some of the observed anomalies were: unfocused spindle poles, malformed spindles (twisted-spindles or curved-spindles) and anaphases with elongated spindles which should have started the constriction of the membrane but are still not advancing to telophase. Mob3 null mutants in Drosophila melanogaster (dMob3) are fertile and viable indicating that this gene is not essential.. It was observed that dMob3 mutants present regions with darker pigmentation, similar to necrotic tissue in various regions of the body. They also present small grey masses resembling tumours. These dMob3 mutants show an accentuated disorientation on the climbing assay. During larval neuroblasts analysis, it was observed a decrease in the size of optical lobes. Mitotic defects were observed, namely the alignment of chromosomes and small defects in the mitotic fuse. Some dMob3 mutant individuals show a white membrane attached to the body which resembles fungi, suggesting the possibility of a weaker immune system. In conclusion, the results from this project suggest that dMob1 might be involved in regulating microtubule dynamics, and dMob3 might be a new tumour suppressor gene, possibly involved in immune response pathways
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Keywords
Ciclo celular dMob1 dMob3 Drosophila melanogaster Dinâmica de microtúbulos Gene supressor de tumores