Research articles

The amount of the BubR1 checkpoint protein declines with age in mouse models, suggesting that it has a role in ageing. Van Deursen and colleagues reveal that expressing a BubR1 transgene in mice reduces tumorigenesis and aneuploidy, and delays ageing-related phenotypes.

The Cdc2 (also called Cdk1) kinase is first activated at the centrosome to initiate mitosis in human cells. Hagan and colleagues demonstrate that in fission yeast, Cdc2 and Polo kinase activation at the spindle pole body remotely controls not only mitotic commitment but also ‘new end take off’, the initiation of bipolar growth in G2.

To segregate chromosomes, spindle microtubules must attach to chromosomes through kinetochores, in a process involving several types of microtubule behaviour. Tolic-Norrelykke and colleagues find that fission yeast microtubules rapidly rotate around the spindle poles, and mathematical modelling confirms that this random microtubule movement facilitates kinetochore capture.

Patterning of Drosophila embryos involves the localization of RNAs to specific places in the oocytes before fertilization. Although both gurken (grk) and bicoid (bcd) mRNA localize to the dorsoanterior of the oocyte, only grk mRNA is translated at this stage. Davis and colleagues find that grk mRNA co-localizes with proteins involved in translation at the periphery of P bodies whereas bcd is enriched into their central region—which the authors show is devoid of ribosomes—where it is translationally repressed.

The mitochondrial calcium uniporter (MCU) mediates calcium uptake by mitochondria and thus regulates cellular bioenergetics, but how MCU activity is modulated is not fully understood. Madesh, Foskett and colleagues report that the integral mitochondrial membrane protein MCUR1 (mitochondrial calcium uniporter regulator 1) binds to the MCU and promotes MCU-dependent calcium uptake to control ATP production and autophagy.

Brown adipose tissue generates heat on exposure to cold temperatures. Stoffel and colleagues identify a cold-regulated pathway that increases levels of the transcriptional regulator Prdm16 to promote brown adipogenesis.

Voinnet and colleagues show that autophagy targets RNAi components DICER and AGO2 for degradation when they are not bound to miRNA. The autophagy receptor NDP52 is required for this homeostatic regulation of the RNAi machinery. The authors also found that autophagy influences the post-translational regulation of DICER mRNA.

Guan and colleagues report that the Hippo pathway effector YAP regulates PI(3)K–mTOR signalling. YAP induces expression of the microRNA miR-29 to block PTEN expression, activating the PI(3)K pathway. Hippo and PI(3)K pathways thus converge to regulate cell growth and proliferation.

Chang and colleagues reveal that the poly(ADP-ribose) polymerase PARP16 participates in the endoplasmic reticulum (ER) stress response. They report that PARP16 is a transmembrane ER protein that PARsylates and activates PERK and IRE1α in response to ER stress.

Notch signalling in the intestinal crypt is modulated to drive commitment to the secretory fate. Clevers and colleagues find that cells expressing the Notch ligand DLL1 are intermediate secretory cells that can revert to Lgr5+ stem cells upon damage.

Persistent ER stress in pancreatic β-cells contributes to the pathogenesis of type 2 diabetes. Fonseca and colleagues show that the ER membrane glycoprotein WFS1, which is mutated in people with Wolfram syndrome, has a known role in the ER stress response. It regulates insulin production and secretion in β-cells by associating with adenylyl cyclase 8 at the plasma membrane and generating cAMP. ER stress prevents WFS1 plasma membrane localization, attenuating cAMP production and insulin secretion.

Intraflagellar transport (IFT) particles are essential for the biogenesis and maintenance of cilia. They assemble at the cilium base and travel up and down the cilia, turning around at the tip, but the mechanisms that regulate these processes were not clear. Hu and colleagues reveal a role for the BBSome in IFT assembly and turnaround.

Membrane deformation is necessary to generate endocytic vesicles, but the molecular mechanisms proposed to drive membrane bending are controversial. Stachowiak and Schmid et al. report that crowding of proteins at the membrane is sufficient to induce curvature in vitro.

Tanentzapf and colleagues use genetic mutations that alter tensile force at the Drosophila myotendinous junction to demonstrate that mechanical force controls in vivo turnover of integrin and intracellular adhesion complexes.

Marine and colleagues use mouse models to show that loss of Dicer or its downstream microRNA cluster miR-17–92 in retinal progenitors prevents retinoblastoma formation through a synthetic lethal interaction with Rb and p53 deficiency.

Shakhova, Sommer and colleagues use mouse models to demonstrate that the Sox10 transcription factor is crucial for the formation and maintenance of giant congenital naevi and melanoma. They show, in human melanoma cells, that Sox10 promotes neural crest stem cell properties, cell proliferation and cell survival.

It is unclear whether proliferating and differentiating cells produce energy through different metabolic pathways. Harris and colleagues show, in the embryonic Xenopus retina, that dividing progenitors use glycogen for glycolysis, and that a transition to oxidative phosphorylation occurs as cells differentiate.

N-BAR-domain-containing proteins regulate membrane dynamics, as they stabilize curved membrane topologies, but whether they primarily sense or generate curvature has remained unclear. Galic, Meyer and colleagues now report that N-BAR proteins accumulate at highly curved membrane areas.

Avidor-Reiss and colleagues show that the nucleotide status of tubulin regulates recruitment of pericentriolar material. Binding of GTP-bound tubulin to the Sas-4 centrosomal protein prevents the Sas-4-dependent formation of centrosomal protein complexes, whereas the Sas-4-stimulated hydrolysis of tubulin–GTP into tubulin–GDP has the opposite effect.

In fission yeast, the septum initiation network (SIN) regulates septation at the end of mitosis. Hagan and colleagues now reveal a further role for the SIN kinase Sid2 that is independent of other known SIN components, in the control of entry into mitosis through phosphorylation of the NIMA kinase Fin1.