Browsing by Author "Duarte, P."
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- A dual function of Drosophila capping protein on DE-cadherin maintains epithelial integrity and prevents JNK-mediated apoptosisPublication . Jezowska, B.; Fernández, B.G.; Amândio, A.R.; Duarte, P.; Mendes, C.; Brás-Pereira, C.; Janody, F.E-cadherin plays a pivotal role in epithelial cell polarity, cell signalling and tumour suppression. However, how E-cadherin dysfunction promotes tumour progression is poorly understood. Here we show that the actin-capping protein heterodimer, which regulates actin filament polymerization, has a dual function on DE-cadherin in restricted Drosophila epithelia. Knocking down capping protein in the distal wing disc epithelium disrupts DE-cadherin and Armadillo localization at adherens junctions and upregulates DE-cadherin transcription. In turn, DE-cadherin provides an active signal, which prevents Wingless signalling and promotes JNK-mediated apoptosis. However, when cells are kept alive with the Caspase inhibitor P35, the activity of the JNK pathway and of the Yorkie oncogene trigger massive proliferation of cells that fail to stably retain associations with their neighbours. Moreover, loss of capping protein cooperates with the Ras oncogene to induce massive tissue overgrowth. Taken together, our findings argue that in some epithelia, the dual effect of capping protein loss on DE-cadherin triggers the elimination of mutant cells, preventing them from proliferating. However, the appearance of a second mutation that blocks cell death may allow for the development of some epithelial tumours
- A mechanism for the elimination of the female gamete centrosome in Drosophila melanogasterPublication . Pimenta-Marques, A.; Bento, I.; Lopes, C. A. M.; Duarte, P.; Jana, S. C.; Bettencourt-Dias, M.An important feature of fertilization is the asymmetric inheritance of centrioles. In most species it is the sperm that contributes the initial centriole, which builds the first centrosome that is essential for early development. However, given that centrioles are thought to be exceptionally stable structures, the mechanism behind centriole disappearance in the female germ line remains elusive and paradoxical. We elucidated a program for centriole maintenance in fruit flies, led by Polo kinase and the pericentriolar matrix (PCM): The PCM is down-regulated in the female germ line during oogenesis, which results in centriole loss. Perturbing this program prevents centriole loss, leading to abnormal meiotic and mitotic divisions, and thus to female sterility. This mechanism challenges the view that centrioles are intrinsically stable structures and reveals general functions for Polo kinase and the PCM in centriole maintenance. We propose that regulation of this maintenance program is essential for successful sexual reproduction and defines centriole life span in different tissues in homeostasis and disease, thereby shaping the cytoskeleton.