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Error-free genome segregation depends on the spindle assembly checkpoint (SAC), a signalling network that delays anaphase onset until chromosomes have established proper spindle attachments. Three reports now quantitatively examine the sensitivity and robustness of the SAC response.
The mTOR protein kinase controls anabolic processes as part of mTOR complexes 1 and 2 (mTORC1 and mTORC2). The two complexes are now shown to be involved in a negative feedback regulatory mechanism, in which mTORC1 stimulation inactivates mTORC2 through the inhibitory phosphorylation of the mTORC2 component Sin1.
In vivo time-lapse imaging and functional tests bring fresh evidence that the morphogen Hedgehog is conveyed to target cells via long filopodia extensions, dubbed cytonemes. This study provides the tools and conceptual framework to understand how cytonemes form and carry morphogens.
Hedgehog (Hh) acts as a morphogen to regulate growth and cell fate specification, and several hypotheses have been proposed for its movement. Using in vivo imaging, Bischoff and colleagues find that cytonemes drive Hh movement in the wing imaginal disc epithelium and that Hh gradient establishment correlates spatially and temporally with cytoneme formation.
Reactivation of fetal gene programs has been linked to hypertrophy of postnatal cardiomyocytes and heart disease, but so far the transcription factors responsible for this effect have not been well defined. De Windt and colleagues have found that the fetal cardiac transcription factor Hand2 is re-expressed in response to stress signalling and induces cardiac hypertrophy.
The microcephaly protein ASPM is required for correct spindle positioning in neuroepithelial cells. Basto and colleagues demonstrate that, in addition to having a role in cell division, the fly ASPM orthologue Asp is important for the maintenance of neuroepithelium integrity by mediating myosin II apico-basal polarity.
Devreotes and colleagues analyse cytoskeletal regulator and signal transduction networks and use computational simulations to provide a model for cell migration. They propose that activation of an excitable signalling network needs to engage an oscillatory cytoskeletal network to promote formation of large protrusions and cell motility.
Schiebel and colleagues use in vitro techniques and yeast genetics to study the role of GTP binding in the microtubule nucleation activity of γ-tubulin.
Hauf and colleagues modulate the amount of spindle assembly checkpoint (SAC) proteins in fission yeast, revealing that a small reduction can cause checkpoint errors. However, levels of critical proteins normally show little variation, which explains the robustness of the SAC.
Wei and colleagues report that phosphorylation of Sin1 by S6K or Akt results in its dissociation from mTORC2, thus suppressing mTORC2 activity. A cancer-patient-derived Sin1 mutation that impairs this phosphorylation leads to mTORC2 hyperactivation and increased tumour formation in mice.
Aguirre-Ghiso and colleagues report that the intensity of TGF-β2 signalling dictates dormancy or metastatic growth of disseminated tumour cells by regulating the activity of p38α/β in different target organs.
During vertebrate embryogenesis, the pharyngeal arch arteries (PAA) connect segments of the primitive circulation. Burns and colleagues show that Nkx2.5+ heart precursors from the lateral plate mesoderm surprisingly give rise to the PAA angioblasts, and that Nkx2.5 is required for PAA development.
The spindle assembly checkpoint (SAC) arrests cells in metaphase until all chromosomes are attached to the spindle. Dick and Gerlich used laser microsurgery to detach individual chromosomes, revealing that the SAC does not have a switch-like response — instead, SAC strength depends on the number of unattached chromosomes.
The spindle assembly checkpoint (SAC) keeps the APC/C ubiquitin ligase inactive until all chromosomes are attached to the spindle. Pines and colleagues tagged endogenous cyclin A with a fluorescent protein by gene targeting and used cyclin A degradation as an assay for SAC activity. They found that the SAC does not show an all-or-nothing response—instead, SAC strength depends on the amount of MAD2 (a checkpoint protein) at kinetochores.
