RESUMO
The proto-oncogenic kinase Abelson (Abl) regulates actin in response to cell signaling. Drosophila Abl is required in the nervous system, and also in epithelial cells, where it regulates adherens junction stability and actin organization. Abl acts at least in part via the actin regulator Enabled (Ena), but the mechanism by which Abl regulates Ena is unknown. We describe a novel role for Abl in early Drosophila development, where it regulates the site and type of actin structures produced. In Abl's absence, excess actin is polymerized in apical microvilli, whereas too little actin is assembled into pseudocleavage and cellularization furrows. These effects involve Ena misregulation. In abl mutants, Ena accumulates ectopically at the apical cortex where excess actin is observed, suggesting that Abl regulates Ena's subcellular localization. We also examined other actin regulators. Loss of Abl leads to changes in the localization of the Arp2/3 complex and the formin Diaphanous, and mutations in diaphanous or capping protein beta enhance abl phenotypes.
Assuntos
Actinas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila , Drosophila melanogaster/embriologia , Embrião não Mamífero/embriologia , Proteínas Proto-Oncogênicas c-abl/metabolismo , Fatores de Despolimerização de Actina , Proteína 2 Relacionada a Actina , Actinas/genética , Animais , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Diferenciação Celular/genética , Proteínas de Ligação a DNA/genética , Destrina , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Forminas , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Microvilosidades/metabolismo , Microvilosidades/ultraestrutura , Mutação/genética , Fenótipo , Transporte Proteico/fisiologia , Proteínas Proto-Oncogênicas c-abl/genéticaRESUMO
Cell and tissue integrity requires the coordination of actin and microtubules and the linkage of these cytoskeletal elements to cell junctions. New findings reveal that the cytoskeletal linker protein Short stop works with EB1 and APC1 to help carry out this function.
Assuntos
Citoesqueleto/fisiologia , Proteínas de Drosophila/metabolismo , Proteínas dos Microfilamentos/metabolismo , Animais , Citoesqueleto/metabolismo , Drosophila , Junções Intercelulares/fisiologia , Microtúbulos/metabolismo , Modelos BiológicosRESUMO
The regulation of signal transduction plays a key role in cell fate choices, and its disregulation contributes to oncogenesis. This duality is exemplified by the tumor suppressor APC. Originally identified for its role in colon tumors, APC family members were subsequently shown to negatively regulate Wnt signaling in both development and disease. The analysis of the normal roles of APC proteins is complicated by the presence of two APC family members in flies and mice. Previous work demonstrated that, in some tissues, single mutations in each gene have no effect, raising the question of whether there is functional overlap between the two APCs or whether APC-independent mechanisms of Wnt regulation exist. We addressed this by eliminating the function of both Drosophila APC genes simultaneously. We find that APC1 and APC2 play overlapping roles in regulating Wingless signaling in the embryonic epidermis and the imaginal discs. Surprisingly, APC1 function in embryos occurs at levels of expression nearly too low to detect. Further, the overlapping functions exist despite striking differences in the intracellular localization of the two APC family members.
