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Wu and colleagues report that under hypoxic conditions the LATS2 kinase is targeted for degradation by the SIAH2 ubiquitin ligase, leading to inhibition of the Hippo kinase cascade and activation of YAP, which promotes tumour growth.
Saurin, Kops and colleagues suggest that rapid spindle assembly checkpoint (SAC) responsiveness is mediated by a mechanism in which active SAC recruits PP2A, leading to PP1 recruitment, which in turn displaces PP2A and shuts off the SAC.
By live imaging and laser microsurgery, Maiato and colleagues characterize how the chromokinesin, dynein and CENP-E motor proteins cooperate to congress chromosomes peripheral to the spindle poles of the metaphase plate in mitosis.
Furuta and colleagues report that single dynein molecules are kept in an autoinhibited state through the stacking of their two head domains. This autoinhibition is relieved when dynein molecules assemble together on cargo.
Yamada and colleagues report that the interaction of the β-Pix guanine exchange nucleotide factor with the GTPase activating protein, srGAP1, regulates cell migration through collagen by activating Cdc42 and suppressing RhoA activity.
Generation of functional T-cells for therapeutic purposes requires a thymic epithelium. Blackburn and colleagues show that FOXN1 expression in fibroblasts triggers the formation of functional thymic epithelial cells that support T-cell differentiation from haematopoietic progenitors.
Hengartner and colleagues use an RNAi-based screening approach in C. elegans to identify effectors of the chemotherapy drug vincristine. They report that the drug induces apoptosis by targeting a conserved LET-99–GPA-11–JNK1 pathway.
The motor protein dynein binds growing microtubule ends, but how it is recruited to plus ends has not been clear. Using in vitro reconstitution and TIRF microscopy, Surrey and colleagues identify a recruitment pathway in which the plus-end binding protein EB1 binds CLIP-170, which in turn recruits the p150 dynein subunit.
Gundersen and colleagues report that the FHOD1 formin is involved in nuclear positioning, by physically linking nesprin-2G, a protein of the outer nuclear membrane, to actin cables, to allow the formation of the transmembrane actin-associated nuclear (TAN) lines that are needed to move the nucleus.
Jones and colleagues combine lineage tracing experiments, chemical carcinogenesis assays and mathematical modelling to study field change development in a preneoplastic epithelium. They demonstrate that Notch pathway inhibition in oesophageal epithelial progenitor cells results in imbalanced differentiation, and mutant clone expansion and dominance in the epithelium, increasing the likelihood of transformation.
The zebrafish trunk has a repetitive pattern of dark stripes and light interstripes, arising from the distribution of distinct pigment cells. Nusslein-Volhard and colleagues have traced clones of pigment cells to show that iridophores forming the interstripes emerge from the dorsal root ganglia into the myoseptum, from where they proliferate and spread. The melanophores themselves appear in situ in between these regions to form the stripes.
The dynein microtubule motor drives the motility of cilia and flagella, but exactly how dynein power strokes are generated is unclear. Using cryo-electron tomography to study intact flagella, Nicastro and colleagues provide structural insights into the power-stroke cycle.
Increased visceral adipose tissue has been associated with metabolic dysfunction but the origin of the progenitors that give rise to this tissue, and whether they are the same as the progenitors contributing to the protective subcutaneous adipose tissue, was unclear. Hastie and colleagues have found that Wt1-positive mesothelial cells contribute to visceral adipocytes.
Burridge and colleagues demonstrate that isolated nuclei respond to force by increasing their stiffness, and that this mechanical adaptation is mediated by emerin phosphorylation.
N6-methyladenosine (m6A) is an abundant internal modification of messenger RNA (mRNA) that has been reported recently in thousands of mammalian mRNAs and long non-coding RNAs (lncRNAs). Zhao and colleagues identify two methyltransferases responsible for this modification in mammalian cells, and demonstrate that they are required for embryonic stem cell self-renewal maintenance through an effect of the modification on the degradation of developmental regulator transcripts.