Articles in 2013

Camargo and colleagues employed an RNAi screen to identify LKB1 as an upstream regulator of the Hippo pathway. They show that LKB1 regulates SCRIB localization through the MARK kinase, leading to regulation of the activity of YAP through MST1/2 kinases.

Auxin signalling controls events in plant development, but it is unclear how auxin sensitivity is regulated. Hwang and colleagues find that phosphorylation of AUXIN RESPONSE FACTORS (ARFs) by BRASSINOSTEROID-INSENSITIVE 2 (BIN2) suppresses their interaction with the repressors AUX/IAA to enhance the transcription of auxin target genes, which is essential for lateral root emergence.

Rab GTPases are important mediators of vesicle trafficking, but how they are regulated is not clear. Thompson and colleagues find that calcium efflux through the ion channel P2XA in the Dictyostelium discoideum contractile vacuole leads to activation of the Rab GTPase-activating protein CnrF, which in turn inactivates Rab11a to allow vacuole fusion.

Lowry and colleagues report the potential role of stem cell quiescence as a tumour suppressive mechanism. They show that although hair follicle stem cell activation allows tumour formation in response to oncogenic stimuli, tumours are not initiated during the quiescent phase of the hair cycle. They further find that the presence of Pten is important in maintaining hair follicle stem cell quiescence in this setting.

Data suggest that autophagy, a process normally associated with cell survival, also promotes cell death, depending on the stimulus or cell type. Thorburn and colleagues find that differences in basal autophagy levels in cells determine survival or death in response to death receptor activation, through modulation of Fap-1 degradation.

Liu and colleagues find that MLKL translocates to the plasma membrane to induce TNF-induced necroptosis, possibly through an effect on calcium influx and the action of the cation channel TRPM7.

In bacteria, the tubulin-related GTPase FtsZ and the actin-related protein FtsA cooperate to form the Z-ring required for cytokinesis. Loose and Mitchison now show that FtsZ and FtsA can self-organize into dynamic structures in vitro, providing insights into the potential regulatory interplay of the two proteins.

How misfolded proteins are extracted from the endoplasmic reticulum (ER) for degradation remains unclear. Sommer and colleagues demonstrate that following assembly into the HRD ligase complex, Der1 forms oligomers in the ER membrane and enables extraction of proteins from the ER lumen.

To delineate the characteristics of lineage emergence in the early mammalian embryo, Hiiragi and colleagues analyse the expression profiles of single cells of the inner cell mass as they differentiate into pluripotent epiblast and primitive endoderm. They observe that cells with initially indistinguishable expression profiles, but exhibiting apparently stochastic differences, resolve into distinct lineages in the late blastocyst through the action of Fgf4.

The oocyte environment is critical for its development. Conti and colleagues demonstrate that, in mouse, amphiregulin-stimulated somatic cumulus cells promote translation of maternal mRNAs in the oocyte in a manner dependent on oocyte PI(3)K signalling.

It has been unclear how round cells elongate during mouse embryo compaction. Plachta and colleagues use live imaging to demonstrate that E-cadherin-dependent filopodia extend to neighbouring cells to drive elongation and compaction.

Cancer is associated with altered DNA methylation. Using whole-genome single-nucleotide sequencing, Adams and colleagues reveal that senescent cells, as well as cells that have bypassed senescence through p53 and pRB inactivation, exhibit methylation changes similar to those seen in cancer.

The stability of the PTEN tumour suppressor protein is regulated by polyubiquitylation. Ma and colleagues identify USP13 as an enzyme reversing polyubiquitylation of PTEN, leading to PTEN stabilization and tumour suppression.

How centrioles are amplified to produce multicilia is unclear, but a structure named the deuterosome has been implicated in the process. Zhu and colleagues demonstrate that Deup1, a paralogue to the centriole protein Cep63, governs deuterosome formation and mediates large-scale de novo centriole amplification in multiciliated cells.

Obesity results from accumulation of white adipose tissue, whereas brown adipose tissue can counteract these effects through thermogenesis. Ning and colleagues have found that the GPCR family member Lgr4 controls the balance between brown and white adipose tissue. In its absence, mice have reduced adiposity and obesity symptoms, and exhibit an increase in brown-like adipocytes, possibly the result of a decrease in Rb expression.

Terman and colleagues employed a genetic screen in Drosophila to identify the SelR methionine sulfoxide reductase as the enzyme responsible for reversing the Mical-mediated oxidation of actin. Thus, SelR antagonizes the effects of Semaphorin–Plexin–Mical-dependent signalling in vivo.

As epithelial tissue spreads during development and wound healing, epithelial integrity needs to be maintained. Heisenberg and colleagues show that tension modulates cell division orientations during zebrafish epiboly through cell elongation and control of myosin II activity to prevent cell fusion and epithelial disruption.

Until the recent discovery of the mitochondrial calcium uniporter (MCU), the effect of increases in mitochondrial calcium levels could not be tested in vivo. Finkel and colleagues have knocked out the gene coding for MCU in adult mice, and show that MCU is required for transport of calcium into the mitochondria. They also show that, in its absence, the function of skeletal muscle is altered; however, surprisingly, no effects are observed on the sensitivity to cell-death-inducing agents.

In an insertional mutagenesis screen, Sabatini and colleagues identify the small G protein ARF4 as a mediator of cell death in response to brefeldin A (BFA) treatment. BFA-induced Golgi stress upregulates ARF4, and loss of ARF protects against propagation of pathogens known to induce Golgi fragmentation.

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.