16 documents found, page 1 of 2
aPKC regulates apical constriction to prevent tissue rupture in the Drosophila ...
Osswald, M; Barros-Carvalho, A; Carmo, AM; Loyer, N; Gracio, PC; Sunkel, CE; Homem, CCF; Januschke, J; Morais-de-Sá, EApical-basal polarity is an essential epithelial trait controlled by the evolutionarily conserved PAR-aPKC polarity network. Dysregulation of polarity proteins disrupts tissue organization during development and in disease, but the underlying mechanisms are unclear due to the broad implications of polarity loss. Here, we uncover how Drosophila aPKC maintains epithelial architecture by directly observing tissue ...
Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut
Brás, R; Monteiro, A; Sunkel, CE; Resende, LPAneuploidy has been strongly linked to cancer development, and published evidence has suggested that aneuploidy can have an oncogenic or a tumor suppressor role depending on the tissue context. Using the Drosophila midgut as a model, we have recently described that adult intestinal stem cells (ISCs), do not activate programmed cell death upon aneuploidy induction, leading to an increase in ISC proliferation rat...
PP1-Mediated Dephosphorylation of Lgl Controls Apical-basal Polarity
Moreira, S; Osswald, M; Ventura, G; Gonçalves, M; Sunkel, CE; Morais-de-Sá, EApical-basal polarity is a common trait that underlies epithelial function. Although the asymmetric distribution of cortical polarity proteins works in a functioning equilibrium, it also retains plasticity to accommodate cell division, during which the basolateral determinant Lgl is released from the cortex. Here, we investigated how Lgl restores its cortical localization to maintain the integrity of dividing e...
Aneuploidy in intestinal stem cells promotes gut dysplasia in Drosophila
Resende, LP; Monteiro, A; Brás, R; Lopes, T; Sunkel, CEAneuploidy is associated with different human diseases including cancer. However, different cell types appear to respond differently to aneuploidy, either by promoting tumorigenesis or causing cell death. We set out to study the behavior of adult Drosophila melanogaster intestinal stem cells (ISCs) after induction of chromosome missegregation either by abrogation of the spindle assembly checkpoint or through ki...
Protein Phosphatase 1 inactivates Mps1 to ensure efficient Spindle Assembly Che...
Moura, M; Osswald, M; Leça, N; Barbosa, J; Pereira, AJ; Maiato, H; Sunkel, CE; Conde, CFaithfull genome partitioning during cell division relies on the Spindle Assembly Checkpoint (SAC), a conserved signaling pathway that delays anaphase onset until all chromosomes are attached to spindle microtubules. Mps1 kinase is an upstream SAC regulator that promotes the assembly of an anaphase inhibitor through a sequential multi-target phosphorylation cascade. Thus, the SAC is highly responsive to Mps1, w...
Genome-wide RNAi screen for synthetic lethal interactions with the C. elegans k...
Maia, AF; Tanenbaum, ME; Galli, M; Lelieveld, D; Egan, DA; Gassmann, R; Sunkel, CE; den, Heuvel, S; Medema, RHKinesins are a superfamily of microtubule-based molecular motors that perform various transport needs and have essential roles in cell division. Among these, the kinesin-5 family has been shown to play a major role in the formation and maintenance of the bipolar mitotic spindle. Moreover, recent work suggests that kinesin-5 motors may have additional roles. In contrast to most model organisms, the sole kinesin-...
Aurora A triggers Lgl cortical release during symmetric division to control pla...
Carvalho, CA; Moreira, S; Ventura, G; Sunkel, CE; Morais-de-Sá, EMitotic spindle orientation is essential to control cell-fate specification and epithelial architecture. The tumor suppressor Lgl localizes to the basolateral cortex of epithelial cells, where it acts together with Dlg and Scrib to organize apicobasal polarity. Dlg and Scrib also control planar spindle orientation, but how the organization of polarity complexes is adjusted to control symmetric division is large...
Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator
Lince-Faria, M; Maffini, S; Orr, B; Ding, Y; Florindo, C; Sunkel, CE; Tavares, Á; Johansen, J; Johansen, KM; Maiato, HA putative spindle matrix has been hypothesized to mediate chromosome motion, but its existence and functionality remain controversial. In this report, we show that Megator (Mtor), the Drosophila melanogaster counterpart of the human nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived...
Dynein and Mast/Orbit/CLASP have antagonistic roles in regulating kinetochore-m...
Reis, R; Feijão, T; Gouveia, S; Pereira, AJ; Matos, I; Sampaio, P; Maiato, H; Sunkel, CEEstablishment and maintenance of the mitotic spindle requires the balanced activity of microtubule-associated proteins and motors. In this study we have addressed how the microtubule plus-end tracking protein Mast/Orbit/CLASP and cytoplasmic dynein regulate this process in Drosophila melanogaster embryos and S2 cells. We show that Mast accumulates at kinetochores early in mitosis, which is followed by a polewar...
Dual Role of Topoisomerase II in Centromere Resolution and Aurora B Activity
Coelho, PA; Queiroz-Machado, J; Carmo, AM; Moutinho-Pereira, S; Maiato, H; Sunkel, CEChromosome segregation requires sister chromatid resolution. Condensins are essential for this process since they organize an axial structure where topoisomerase II can work. How sister chromatid separation is coordinated with chromosome condensation and decatenation activity remains unknown. We combined four-dimensional (4D) microscopy, RNA interference (RNAi), and biochemical analyses to show that topoisomera...