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It is not fully understood how polyploidy is regulated in mammals, as the liver is one of only a few tissues in which it occurs. De Bruin and colleagues demonstrate that gene repression through the E2F8 transcription factor, antagonized by E2F1, is required for polyploidization in mice. They also find that loss of polyploidy does not influence liver differentiation or regeneration.
Wagner and colleagues show that cancer cell survival during liver cancer initiation depends on inhibition of c-Fos-induced apoptosis, through the repression of survivin expression by c-Jun and SIRT6.
Tumbarello, Buss and colleagues report that the motor protein myosin VI has an important role in autophagosome maturation. They show that myosin VI binds to autophagy adaptors to mediate delivery of endocytic cargo and endosomal membrane to autophagosomes, and promote autophagosome–lysosome fusion.
Giannone and colleagues use super-resolution microscopy to analyse the nanoscale dynamic organization of talin and integrins β1 and β3 in focal adhesions.
Fox and colleagues report that VEGF-A stimulation of endothelial cells induces the phosphorylation of profilin by VEGFR2 and Src. This regulation promotes endothelial cell migration and angiogenesis in mice facing pathological conditions such as tissue wounding and ischaemic injury.
Goldman and colleagues report that the transcriptional repressor Insm1a is essential for retinal regeneration following injury in fish. Insm1a suppresses the expression of Ascl1a to promote Müller glial cells’ dedifferentiation at early stages of regeneration, and defines the regeneration zone by negatively regulating the expression of the heparin-binding EGF. It also halts the proliferation of retinal progenitors in the late stages of the process.
During cytokinesis, the intercellular bridge connecting the mother and daughter cell is thinned by a process called secondary ingression before it is eventually severed in an ESCRT-III-dependent manner. Prekeris and colleagues report that FIP3-positive endosomes deliver p50RhoGAP and SCAMP2/3 proteins to the intercellular bridge, which promote actin depolymerization to decrease the bridge diameter and allow ESCRT-III binding.
In a quantitative proteomics approach, Mailand, Choudhary and colleagues characterize ultraviolet-regulated ubiquitylation sites and identify a role for double mono-ubiquitylation of PCNA-associated factor PAF15 in bypassing replication-blocking lesions in DNA.
The mechanisms that control intracellular Wnt trafficking and secretion are beginning to be unravelled. However, little is known about how Wnt proteins are transported once they reach extracellular space. Boutros and colleagues show that active Wnt proteins are secreted on exosomes from Drosophila and human cells, and provide insight into the cellular machinery that regulates their transport and release.
Bennett and colleagues find that auxin modulates water uptake in Arabidopsis roots by negatively regulating the expression of water channel aquaporins to allow lateral root emergence. The functional importance of aquaporins is supported by a mathematical model that shows delayed lateral root emergence when aquaporin levels are perturbed, as well as by the effects observed after aquaporin overexpression or mutation.
Cai and colleagues show that the function of adult hypothalamic neural stem cells in mice is impaired following NF-κB activation associated with a chronic high-fat diet, resulting in development of obesity and neurodegenerative features. Mechanistically, NF-κB affects both Notch signalling and apoptosis in these cells.
In plants, the heterotrimeric G-protein α subunit is kept inactive by binding to the regulator of G protein signalling 1 (RGS1) protein. Jones and colleagues show that G-protein β and γ subunits recruit the WNK8 kinase to the plasma membrane, where WNK8 phosphorylates RGS1 and facilitates its internalization. This effect de-represses Gα signalling and is required for sugar signalling and cell proliferation.
The CDKL5 kinase is mutated in several neurodevelopmental disorders. Broccoli and colleagues find that CDKL5 regulates dendritic spine formation by phosphorylating the adhesion molecule NGL-1, which acts on synaptic contacts. They also show that neurons (derived from induced pluripotent stem cells) from patients carrying the CDKL5 mutation have aberrant dendritic spines, similarly to rodents with impaired CDKL5 function.
The last step in autophagy involves fusion of autophagosomes with lysosomes to generate autolysosomes. Through proteomics analysis and an RNAi screen, Yu and colleagues provide mechanistic insight into how lysosomes are regenerated from autolysosomes. Their analyses reveal a key role for clathrin and phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) in this process.
By performing a screen for genes that regulate epithelial architecture, Martín–Belmonte and colleagues identify key roles for the synaptotagmin-like proteins Slp2-a and Slp4-a in restricting lumen generation. They find that Slp2-a targets Rab27a/b-positive vesicles to PtdIns(4,5)P2-enriched apical membranes, whereas Slp4-a controls subsequent vesicle tethering and fusion. Their coordinated activities ensure the creation of a single lumen per cell.
Wang and colleagues have uncovered a direct functional relationship between the brassinosteroid-activated transcription factor BZR1 and the light- and heat-sensitive transcription factor PIF4. This interplay integrates hormonal and environmental signals to modulate cell elongation during plant growth.
Coffer and colleagues report that the transcription factor FOXO3 regulates the induction of autophagy. In response to PI(3)K–Akt signalling, FOXO3 directly induces expression of glutamine synthase, which upregulates glutamine levels and triggers autophagy.
Wang and colleagues show that, in Arabidopsis thaliana, brassinosteroid and light-dependent transcription factors are required for giberellin effects on hypocotyl elongation, by modulating transcription of giberellin-induced genes involved in cell wall synthesis and photosynthesis. Conversely, giberellin relieves the brassinosteroid component BZR1 from inhibition by DELLA proteins.
Microvilli are essential for the function of intestinal cells. Bos and colleagues have found that the polarity kinase LKB-1 induces PtdIns(4,5)P2 enrichment at the apical membrane. This leads to the successive accumulation of phosphatidic acid and the small GTPase Rap2A with its GEF and its effectors. These, in turn, trigger the changes in the actin cytoskeleton responsible for microvilli formation.
Zhang, McNaughton and colleagues show that inflammatory stimuli promote a direct association between the heterotrimeric G-protein subunit Gαq and the temperature-sensitive ion channel TRPM8. This interaction inhibits TRPM8 channel activity, providing a mechanism by which inflammation produces aberrant sensations of temperature changes.
