Volume 16 Issue 12, December 2014

The endoderm layer destined to be primitive gut is a mosaic of earlier visceral endoderm and definitive endoderm that arises later, during gastrulation. Live imaging now reveals that in mouse embryos, definitive endoderm cells egress from underlying mesoderm and intercalate into the overlying cell layer. This process requires SOX17-mediated control of basement membrane organization.

Protein quality control systems protect cells from proteotoxicity caused by the accumulation of aberrantly folded polypeptides. The Rsp5 ubiquitin ligase (mammalian homologue Nedd4) is now identified as a major constituent of a clearance pathway that degrades misfolded cytosolic proteins after exposure to heat.

Autophagy is an intracellular degradation system that is mediated by orchestrated functions of membranes and proteins. A genetic screen in Caenorhabditis elegans revealed that O-linked N-acetylglucosamine modification of the SNARE protein SNAP-29 negatively regulates SNARE-dependent fusion between autophagosomes and lysosomes. This regulatory mechanism is conserved in mammals.

Beachy and colleagues demonstrate that reduced Hedgehog (Hh) signalling at the tips of nascent buds allows stromal production of hepatocyte growth factor (Hgf), whereas in surrounding cells Hh inhibits Hgf through induction of miR-26a and miR-26b.

Using time-lapse imaging Hadjantonakis and colleagues have characterized the intercalation of definitive endoderm progenitors into the overlying visceral endoderm during mouse gastrulation and demonstrated a role for the transcription factor SOX17 in this process.

Kronenberg and colleagues report that mesenchymal progenitor cells in endochondral bones express chondrocyte markers. By lineage tracing, they see that this population contributes to chondrocytes, osteoblasts and stromal cells in postnatal bones.

Schumacher and colleagues find that the FOXO transcription factor DAF-16 is activated in response to DNA damage in C. elegans and promotes developmental growth in a manner involving EGL-27.

Ferroptosis is a form of non-apoptotic cell death with unclear physiological relevance. Conrad and colleagues now report that unrestrained ferroptosis can lead to renal failure. They also identify a small molecule that limits ferroptosis in vivo.

Through biochemical and single-molecule analyses, Vallee, Gross and colleagues characterize how subdomains of the dynactin subunit p150 regulate dynein movement along microtubules.

Dynlacht and colleagues report that Foxk transcription factors inhibit the induction of autophagy by recruiting Sin3A–HDAC complexes to autophagy-promoting genes to limit their expression.

Zhang and colleagues report that starvation reduces O-GlcNAcylation of the SNARE protein SNAP-29. This promotes formation of a competent SNARE complex that increases autophagosome–lysosome fusion, increasing autophagosome maturation and flux.

Mayor and colleagues identify yeast Rsp5 (mammalian homologue Nedd4) as the main ubiquitin ligase responsible for the increased ubiquitylation following heat stress when Rsp5 targets cytosolic misfolded proteins for proteasome degradation.

Clarke and colleagues show that TLR2–MYD88 cancer-cell-intrinsic signalling is involved in mammary and colon epithelial regeneration and tumour formation.

By live imaging and laser microsurgery, Maiato and colleagues characterize how the chromokinesin, dynein and CENP-E motor proteins cooperate to congress chromosomes peripheral to the spindle poles of the metaphase plate in mitosis.

Saurin, Kops and colleagues suggest that rapid spindle assembly checkpoint (SAC) responsiveness is mediated by a mechanism in which active SAC recruits PP2A, leading to PP1 recruitment, which in turn displaces PP2A and shuts off the SAC.