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The centromere-specific histone H3 variant CENP-A is sufficient for centromere specification in many species. Cleveland and colleagues have used an elegant gene targeting strategy to define a two-step mechanism for how CENP-A acts in centromere targeting and kinetochore assembly and function.
In mouse oocytes, Rab11a-positive vesicles are associated with actin nucleators. Schuh and colleagues find that these vesicles function as storage reservoirs for actin nucleators, that the actin network can be modulated by altering the number of Rab11a vesicles, and that actin dynamics affect the positioning of the meiotic spindle.
Surani and colleagues use single-cell transcriptomics analysis in a model of mouse primordial germ cell specification to analyse the collaboration between three transcription factors, BLIMP1, PRDM14 and AP2γ, in determining germ cell fate. They find that BLIMP1 binds directly to repress somatic and cell proliferation genes, and at the same time induces AP2γ, which acts together with PRDM14. The three factors are sufficient for specification and form a tripartite interdependent transcriptional network.
Pellman and colleagues report that the Kip3 kinesin-8 has antiparallel microtubule-sliding activity. The ability of Kip3 to slide antiparallel microtubules, along with its known role in destabilizing microtubules, are important for regulating spindle length.
The ATM checkpoint kinase and the tumour suppressor ARF are thought to act separately to counteract tumorigenesis. Bartek, Gorgoulis and colleagues find that in transformed cells, ATM negatively regulates the levels and activity of ARF. In cell culture and mouse xenograft experiments, ATM inhibition promotes ARF-mediated tumour suppression, demonstrating an interplay between these pathways.
Verlhac, Terret and colleagues report that softening of the mouse oocyte cortex during meiosis I is needed for spindle migration and positioning. They show that Mos/mAPK signalling triggers myosin II exclusion from the cortex and an Arp2/3-dependent cortical F-actin thickening that contributes to cortical softening.
Deficiency in dystrophin leads to death with cardiorespiratory failure in humans, but mice lacking dystrophin have minimal heart defects. Blau and colleagues find that mice that lack dystrophin and have shorter telomeres exhibit cardiac defects similar to human patients, with an increase in oxidative stress. The authors also found that onset of cardiac defects could be delayed by antioxidant treatments and that, strikingly, patients also have shortened telomeres.
Martin and colleagues analyse the mechanism underlying Twist- and Rho1-driven apical constriction of ventral furrow cells in Drosophila. They characterize the spatial localization of the Rho1 effectors Rok1 and Dia, and their effects on the actomyosin network and adherens junctions.
Fetal haematopoietic stem cells (HSCs) display higher self-renewal potential than their adult counterparts. Eaves and colleagues show that adult HSCs express lower levels of Lin28b and higher levels of let-7 miRNA. They demonstrate that Lin28 overexpression, as well as that of Hmga2 (a target of let-7), induces fetal properties in adult HSCs. Conversely, HMGA2 loss in fetal HSCs results in premature induction of adult HSC self-renewal properties.
The p53 homologue TAp73 is frequently overexpressed in tumours, suggesting it provides an advantage to cancer cells. Yang and colleagues have investigated the role of TAp73 in tumour cell proliferation and showed that TAp73, but not p53, is a transcriptional activator of glucose-6-phosphate dehydrogenase. Increased expression of this gene promotes the pentose phosphate pathway flux, leading to enhanced biosynthesis and antioxidant defence, both of which have been shown to support optimal cell proliferation and tumour formation.
Gilson and colleagues report that increased expression of the telomeric protein TRF2 in tumour cells promotes tumorigenesis in a non-cell-autonomous manner, by inhibiting the recruitment and activation of natural killer cells at the tumour site.
Sahai and colleagues present a computational model of cell motility based on experimentally derived parameters. They show that the model predicts the behaviour of cells in in vitro and in vivo settings with respect to the migration strategy and response of cancer cells to specific experimental interventions.
Recovery of neurotransmitter involves the endocytic retrieval of vesicles from the plasma membrane. Jonas and colleagues show that in hippocampal synapses, the anti-apoptotic protein Bcl-xL enhances the recovery of a vesicle pool. It does this independently of its mitochondrial function, through its calmodulin-stimulated translocation to clathrin-coated pits and recruitment of the dynamin-related protein Drp1.
Mayor and colleagues observed that placodal cell movements in Xenopus and zebrafish embryos are controlled by their interaction with adjacent neural crest cells. Neural crest cells chemotactically migrated towards placodal cells and, on contact, induced neural crest cells to migrate away, revealing a ‘chase-and-run’ behaviour.
Chromosome segregation requires the capture of kinetochores by microtubules, a process that in yeast mitosis is facilitated by kinetochores being tethered to spindle poles. Sato and colleagues find that in meiosis I, when kinetochores are not tethered to poles, a microtubule array associated with TACC (Alp7) and TOG proteins (Alp14 and Dis1) retrieves kinetochores in a Polo-kinase-dependent manner.
A property of oncogene-induced senescence (OIS) is the induction of a secretory phenotype, termed the senescence-associated secretome (SASP). Gil and colleagues now provide evidence that senescence can be transmitted in a paracrine manner, by showing that induction of the SASP in cells undergoing OIS by inflammasome-mediated interleukin-1 signalling can promote senescence of normal neighbouring cells.
Bissell, Ghajar and colleagues use organotypic culture systems and in vivo mouse and zebrafish models to reveal the distinct effects of different microvascular niches on tumour cell dormancy. They report that although the stable microvasculature promotes cancer cell quiescence through the production of thrombospondin-1, cancer cells residing near neovascular tips are induced to grow through the action of TGF-β and periostin.
Faessler and colleagues analyse the distinct properties of β1 and αv integrin subclasses, and provide insight into the different protein compositions, signalling activities and contributions to rigidity sensing of adhesion sites anchored by each integrin subtype.
The Emi1 protein inhibits the anaphase promoting complex (APC), an E3 ubiquitin ligase and critical cell cycle regulator, but it has remained unclear how it does this. Wang and Kirschner demonstrate that Emi1 suppresses the elongation of ubiquitin chains on APC substrates by interfering in different ways with the activities of the E2 enzymes UBCH10 and Ube2S.
Pei and colleagues show that introduction of the pluripotency reprogramming factors in sequence (Oct4–Klf4, c-Myc and finally Sox-2), rather than introducing them all together, increases reprogramming efficiency. This sequential delivery activates the epithelial-to-mesenchymal transition (EMT) before the mesenchymal-to-epithelial transition (MET), which was previously reported to occur during reprogramming. The authors also show that addition of EMT modulators influences reprogramming in a similar manner.
