Volume 13 Issue 10, October 2011

Recognizing the importance of sound scientific advice to the government, the UK Parliament has examined the peer review system.

Successful completion of meiosis in vertebrate oocytes requires the localization and maintenance of the meiotic spindle at the cell cortex. Arp2/3-nucleated actin filaments are now shown to flow away from the cortex overlying the spindle, resulting in cytoplasmic streaming, which maintains the spindle in its asymmetric position.

A potential role for glycosphingolipids and lipid rafts in apical sorting was initially met with enthusiasm, but genetic analysis has since provided little support for it. A report now establishes that glycosphingolipids mediate apical sorting, and specifically help maintain apicobasal polarity in Caenorhabditis elegans.

Cell polarity is critically important for organogenesis. Using a series of RNA-interference-based screens, Göbel and colleagues reveal the role of the glycosphingolipid glucosylceramide (GlcCer) in determining apicobasal polarity and maintaining the organization of the intestinal lumen in the developing worm.

Notch and VEGF signalling controls the specification of endothelial cells to tip and stalk cells during angiogenesis sprouting. Alitalo and colleagues show that macrophage-derived VEGF-C activates VEGFR2 to contribute to the conversion of endothelial cells from a tip- to a stalk-cell fate when two sprouts fuse to ensure vessel growth and branching.

Doxsey and colleagues report that midbodies accumulate in stem cells, including induced pluripotent stem cells and potential cancer-initiating cells. Loss of midbodies accompanies stem-cell differentiation and is mediated through binding of the autophagy receptor NBR1 to the midbody protein CEP55. Downregulation of NBR1 is associated with enrichment of midbodies, enhanced reprogramming and increased tumorigenicity in cancer cells.

ATP production by mitochondria requires the efficient flow of protons through the F₁F_O ATP-synthase complex. Jonas and colleagues show that Bcl-xL interacts with the F₁F_O complex in the mitochondrial matrix and increases the efficiency of this enzyme by decreasing proton leak.

The spindle assembly checkpoint halts cell-cycle progression in the presence of unattached kinetochores by preventing activation of APC/C. Pines and colleagues find that APC15 has a critical role in regulating APC/C activation by promoting release of the inhibitory MCC complex from APC/C once the spindle assembly checkpoint is satisfied.

Srivastava and colleagues find that membrane-bound Notch associates with and negatively regulates active β-catenin in embryonic stem cells, cardiac progenitors and colon cancer cells. This ligand-independent effect of Notch requires the endocytic adaptor protein Numb and targeting of β-catenin to lysosomes.

Mammalian oocyte maturation involves two asymmetric meiotic divisions that require the positioning of the meiotic spindle near the cortical area from which the extrusion of the polar bodies occurs. Li and colleagues show that the nucleating activity of the Arp2/3 complex, localized at the cortical actin cap, induces actin-filament flow away from the complex, creating a cytoplasmic streaming that pushes the spindle towards the cortex.

Overlapping antiparallel microtubules are important in cellular structures such as the mitotic spindle. Diez and colleagues use an in vitro system and mathematical modelling to show that the formation of stable overlaps involves a motor such as kinesin-14, which slides microtubules apart, and a passive microtubule crosslinker, Ase1, which accumulates at microtubule overlapping regions and slows microtubule sliding to prevent their separation.

The microtubules that attach kinetochores to chromosomes (K-fibres) are stabilized in prometaphase to allow for accurate chromosome segregation. Kapoor and colleagues find that the B56-PP2A phosphatase stabilizes K-fibres potentially by counteracting the phosphorylation of kinetochore substrates that is mediated by Aurora B and Plk1.

Franzoso and colleagues show that NF-κB protects cells from nutrient-starvation-induced necrosis by upregulating mitochondrial respiration through increased p53-dependent expression of the SCO2 enzyme. Conversely, inhibition of NF-κB results in increased aerobic glycolysis, known as the Warburg effect, thus promoting oncogenic transformation, and affects metabolic adaptation during tumorigenesis in vivo.

The maintenance of genomic integrity requires tight control of the cell division process as well as accurate repair of damaged DNA, and failure in such mechanisms can cause developmental disorders and cancer. In the October issue of Nature Cell Biology, leading scientists highlight and discuss new developments in these areas.