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Publication
Proliferação celular na ausência de função do gene Mob3
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Advisor(s)
Abstract(s)
O desenvolvimento e a manutenção dos organismos dependem do equilíbrio entre a proliferação celular e a apoptose, essenciais à morfogénese e ao crescimento dos tecidos. Este equilíbrio é controlado por várias vias de sinalização, incluindo a via Hippo, cuja atividade é modulada por proteínas da família Mob. Além de regular negativamente a atividade da via Hippo, dados preliminares sugerem que, em células humanas, o MOB4 tem um papel essencial na progressão da mitose. Adicionalmente, estudos mostraram uma expressão elevada dos genes MOB3 e MOB4 em tumores humanos. Desta forma, o principal objetivo deste projeto foi estudar a função molecular dos genes Mob3 e Mob4 na proliferação celular, utilizando a Drosophila melanogaster. Começou-se por seguir a localização subcelular da proteína GFP-Mob3 durante a mitose, em neuroblastos larvares. Além disso, foram analisados os efeitos mitóticos, provocados pela ausência do Mob3, em cérebros larvares de indivíduos nulos Mob3. Observou-se que a localização intracelular da proteína Mob3 é constante nos vários estadios de desenvolvimento da mosca, sugerindo uma função conservada desta proteína. Os indivíduos nulos Mob3 revelaram ainda problemas na proliferação celular, evidenciados pela redução do
tamanho dos cérebros larvares e do número de mitoses. Estes indivíduos apresentaram também problemas na segregação do DNA. No Mob4, a abordagem adotada consistiu na observação dos fenótipos no indivíduo adulto e na análise dos efeitos mitóticos, provocados pela depleção específica do Mob4 em três tecidos larvares diferentes, utilizando o sistema UAS-Gal4. Analisou-se ainda a atividade desta proteína como um potencial componente do complexo STRIPAK. A depleção do Mob4 resultou numa diminuição do tamanho dos tecidos selecionados. Observou-se ainda uma diminuição do número de células em mitose e um aumento da apoptose. Em conjunto, os nossos dados sugerem uma função conservada do Mob4, enquanto elemento do complexo STRIPAK, na manutenção do equilíbrio entre a proliferação e a apoptose. Além disso, o Mob4 parece ser necessário ao correto estabelecimento da polaridade nos tecidos, observando-se uma desorganização no posicionamento das células nos tecidos com depleção do Mob4.
Em suma, os nossos dados sugerem que os genes Mob3 e Mob4 são essenciais ao controlo da proliferação celular.
The development and maintenance of organisms depends on the balance between cell proliferation and apoptosis, which are essential for morphogenesis and tissue growth. This balance is regulated by various signaling pathways, including the Hippo pathway, whose activity is modulated by proteins from the Mob family. In addition to negatively regulating the activity of the Hippo pathway, preliminary data suggest that, in human cells, MOB4 plays an essential role in the progression of mitosis. Furthermore, studies have shown an elevated expression of the MOB3 and MOB4 genes in human tumors. Therefore, the primary objective of this project was to study the molecular functions of the Mob3 and Mob4 genes in cell proliferation, using Drosophila melanogaster. We started by following the subcellular localization of the GFP-Mob3 protein during mitosis in larval neuroblasts. Additionally, we analyzed the mitotic effects caused by the absence of Mob3 in larval brains of Mob3 null individuals. We found that the intracellular localization of the Mob3 protein remains constant throughout the various stages of fly development, suggesting a conserved function for this protein. Mob3 null individuals also showed defects in cell proliferation, reflected by a reduction in larval brain size and the number of mitoses. These individuals also exhibited problems with DNA segregation. For Mob4, the approach adopted involved the observation of phenotypes in the adult individual and the analysis of mitotic effects caused by the specific depletion of Mob4 in three different larval tissues, using the UAS-Gal4 system. We also analyzed Mob4 protein activity as a potential component of the STRIPAK complex. Mob4 depletion resulted in a reduction in the size of selected tissues. Additionally, there was a decrease in the number of cells in mitosis and an increase in apoptosis. Together, the data suggest a conserved role for Mob4, as part of the STRIPAK complex, in maintaining the balance between proliferation and apoptosis. Furthermore, Mob4 appears to be required for the correct establishment of tissue polarity, as disorganization in cell positioning was observed in Mob4 depleted tissues. In summary, our data suggest that Mob3 and Mob4 genes are essential for controlling cell proliferation.
The development and maintenance of organisms depends on the balance between cell proliferation and apoptosis, which are essential for morphogenesis and tissue growth. This balance is regulated by various signaling pathways, including the Hippo pathway, whose activity is modulated by proteins from the Mob family. In addition to negatively regulating the activity of the Hippo pathway, preliminary data suggest that, in human cells, MOB4 plays an essential role in the progression of mitosis. Furthermore, studies have shown an elevated expression of the MOB3 and MOB4 genes in human tumors. Therefore, the primary objective of this project was to study the molecular functions of the Mob3 and Mob4 genes in cell proliferation, using Drosophila melanogaster. We started by following the subcellular localization of the GFP-Mob3 protein during mitosis in larval neuroblasts. Additionally, we analyzed the mitotic effects caused by the absence of Mob3 in larval brains of Mob3 null individuals. We found that the intracellular localization of the Mob3 protein remains constant throughout the various stages of fly development, suggesting a conserved function for this protein. Mob3 null individuals also showed defects in cell proliferation, reflected by a reduction in larval brain size and the number of mitoses. These individuals also exhibited problems with DNA segregation. For Mob4, the approach adopted involved the observation of phenotypes in the adult individual and the analysis of mitotic effects caused by the specific depletion of Mob4 in three different larval tissues, using the UAS-Gal4 system. We also analyzed Mob4 protein activity as a potential component of the STRIPAK complex. Mob4 depletion resulted in a reduction in the size of selected tissues. Additionally, there was a decrease in the number of cells in mitosis and an increase in apoptosis. Together, the data suggest a conserved role for Mob4, as part of the STRIPAK complex, in maintaining the balance between proliferation and apoptosis. Furthermore, Mob4 appears to be required for the correct establishment of tissue polarity, as disorganization in cell positioning was observed in Mob4 depleted tissues. In summary, our data suggest that Mob3 and Mob4 genes are essential for controlling cell proliferation.
Description
Keywords
Proliferação celular Mitose Complexo stripak