Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
FOXO transcription factors promote longevity from worms to mammals, but the mechanisms by which FOXO extends lifespan have remained elusive. In the nematode Caenorhabditis elegans, FOXO is now shown to recruit the nucleosome remodelling complex SWI/SNF to its target genes, which is essential for FOXO to elicit stress resistance and longevity.
Sorting nexin proteins (SNXs) and the cargo-selective retromer complex play key roles in receptor recycling from endosomes to the cell surface. A global proteomics analysis reveals a collection of cell surface proteins that rely on SNX27 and the retromer complex for their cell surface localization at steady state.
Notch signalling modulates fate decisions in stem and progenitor cells in various tissues. Artavanis-Tsakonas and colleagues use in vivo genetic labelling to uncover cell progenitors that are implicated in mammary gland branching and alveolar formation.
Internalized transmembrane proteins can be recycled to the plasma membrane by SNX27–retromer-mediated transport. Cullen and colleagues have done a global analysis of retromer-mediated transport by combining quantitative proteomics to delineate the SNX27 interactome and an analysis of the surface proteome of SNX27- or retromer-suppressed cells. They show that the SNX27–retromer complex recycles proteins involved in maintaining cellular nutrient homeostasis and is required to prevent lysosomal degradation of the recycling cargoes.
Phosphatidylinositol-3-OH kinase (PI(3)K) signalling regulates many cellular events such as cell growth and survival. Pagano and colleagues show that the E3 ligase SCF-FBXL2 promotes PI(3)K signalling and inhibits autophagy by targeting the free p85β subunit of the p110–p85 PI(3)K complex for degradation.
In the presence of stress stimuli, the endoplasmic reticulum either adapts the protein synthesis or triggers an apoptotic response, but the mechanisms underlying this decision are unknown. Kaufman and colleagues show that the ER stress response factors ATF4 and CHOP increase protein synthesis, which in turn induces oxidative stress and increased ATP consumption, leading to cell death during chronic ER stress.
FOXO transcription factors confer stress resistance and longevity in several organisms. Ruvkun and colleagues demonstrate in Caenorhabditis elegans that DAF-16 (FOXO homologue) recruits the chromatin remodeller SWI/SNF to target genes. They show that SWI/SNF is required for DAF-16-mediated functions such as dauer formation, stress resistance and increasing longevity.
Haematopoietic stem cells (HSCs) emerge from a specialized population of endothelial cells, but the events that trigger the transition from endothelial to haemogenic fate are still unclear. Keller and colleagues identified Sox17 as a regulator of this transition upstream of the Notch signalling pathway. They showed that Sox17–GFP marks emerging HSCs in embryo development and when differentiating from mouse embryonic stem cells.
The mechanism of tissue maintenance in the tongue is unclear. Ueno and colleagues define Bmi1-positive stem cells in the interpapillary pit of the murine tongue and demonstrate that these cells (which exhibit low proliferative properties at homeostasis) ensure regeneration of the tongue after injury.
Frog embryonic cell cycles are driven by oscillations in the activity of cyclin B–Cdk1. This complex activates the E3 ligase APC/CCdc20, which in turn causes cyclin B degradation, creating a negative feedback loop. Yang and Ferrell combine experimentation and mathematical modelling to demonstrate that the loop functions as a time-delayed ultrasensitive switch that promotes robust oscillations.
The segregase Cdc48 (also called p97 or VCP) extracts ubiquitylated proteins from their environment. Jentsch and colleagues demonstrate that Cdc48 binds SUMOylated Rad52, and removes Rad52 and the recombinase Rad51 from DNA to restrict spontaneous recombination.
Haematopoietic stem and progenitor cells (HSPCs) are found in unique bone marrow microenvironments. Silberstein and colleagues use imaging cytometry to quantitatively determine HSPC distribution in femoral bones. They find that HSPCs are in endosteal zones, in close proximity to specialized microvessels, and that they appear in a hypoxic state whether or not they are close to the vasculature.
