News & Comment

  • News and Views |

    Recycling from endosomes to the plasma membrane is an important step in cell homeostasis. The retromer/SNX27/WASH complex recycles numerous receptors, but key ones are still unaccounted for. Now a related conserved heterotrimer, called retriever, has been identified that, together with SNX17, the CCC complex and WASH, mediates the recycling of α5β1 integrins.

    • Catherine Rabouille
  • News and Views |

    It is generally accepted that protein function depends on a defined 3D structure, with unfolding and aggregation dealing a final blow to functionality. A study now shows that the regulated exposure of an unstructured region in yeast pyruvate kinase triggers reversible aggregation to preserve protein function under stress.

    • Jörg Höhfeld
  • News and Views |

    During muscle development, nuclei travel from the centre of the myofibre to the periphery, a process defective in certain diseases. A new study reveals that this movement is due to centripetal forces imposed on nuclei by the crosslinking and contraction of myofibrils.

    • Jonathan N. Rosen
    •  & Mary K. Baylies
  • News and Views |

    Cancer cells preferentially metastasize to certain organs. A study in mouse models of breast cancer shows that the DKK1 negative regulator of WNT signalling inhibits tropism to the lung, but enhances tropism to the bone due to the differential regulation of canonical and non-canonical WNT signalling in the two microenvironments.

    • Wei Zheng
    •  & Jeffrey W. Pollard
  • News and Views |

    The cytokine tumour necrosis factor (TNF) and the toll-like receptors (TLRs) coordinate immune responses by activating inflammatory transcriptional programs, but these signals can also trigger cell death. Recent studies identify the MAP kinase substrate MK2 as a key player in determining whether cells live or die in response to TNF and TLR signalling.

    • Andrew Oberst
  • News and Views |

    Three-dimensional brain organoid models have come into the spotlight as in vitro tools to recapitulate complex features of the brain. Four recent papers now leverage current technologies to generate new flavours of brain organoids and address aspects of brain biology which, to date, have been challenging to explore.

    • Lin Yang
    •  & Huck-Hui Ng
  • News and Views |

    Cellular senescence, a cell-autonomous growth arrest program, also executes pleiotropic non-cell-autonomous activities through the senescence-associated secretory phenotype (SASP). The innate cGAS–STING DNA-sensing pathway is now shown to regulate senescence by recognizing cytosolic DNA and inducing SASP factors, uncovering an unexpected link between these two previously unrelated pathways.

    • Marina Ruiz de Galarreta
    •  & Amaia Lujambio
  • News and Views |

    Brown adipose tissue is a key metabolic organ that oxidizes fatty acids and glucose to generate heat. Through epigenomic analyses of multiple adipose depots, the transcription factor nuclear factor I-A (NFIA) is now shown to drive the brown fat genetic program through binding to lineage-specific cis-regulatory elements.

    • Suzanne N. Shapira
    •  & Patrick Seale
  • News and Views |

    Induced pluripotent stem cells derived from aged donors (A-iPSCs) usually show genomic instability that affects their utility and raises concerns about their safety. Now, a study highlights the importance of ZSCAN10-dependent recovery of glutathione–ROS homeostasis in counteracting the genomic defects in A-iPSCs.

    • Clea Bárcena
    •  & Carlos López-Otín
  • News and Views |

    Cancer treatments often focus on killing tumour cells through apoptosis, which is thought to typically require mitochondrial outer membrane permeabilization (MOMP) and subsequent caspase activation. A study now shows that MOMP can trigger TNF-dependent, but caspase-independent cell death, suggesting a different approach to improve cancer therapy.

    • Brent E. Fitzwalter
    •  & Andrew Thorburn
  • Editorial |

    Peer review is a key element of scientific publishing. Here we discuss what constitutes the ideal referee report.

  • News and Views |

    CCCTC-binding factor (CTCF) sites are enriched at the boundaries of topologically associated domains (TADs), but their function within TADs is unclear. Removal of sub-TAD CTCF sites adjacent to the α-globin enhancers is now shown to result in inappropriate activation of neighbouring genes. Intra-TAD enhancer insulation might be broadly important for tissue specificity of enhancers.

    • Ivan Krivega
    •  & Ann Dean
  • News and Views |

    Mutations in AT rich interactive domain 1A (ARID1A) are common in ovarian cancers. A study now shows that HDAC6 activity is required for survival of ovarian cancer cells bearing ARID1A mutations. HDAC6 inhibition selectively promotes apoptosis of ARID1A-inactivated cells, supporting the use of HDAC6 inhibition in the treatment of clear cell ovarian cancer.

    • Lucia Altucci
  • News and Views |

    Obesity now rivals smoking as one of the leading preventable causes of cancer. Obesity-associated neutrophilia is now shown to enhance breast cancer metastasis and to be reversible through dietary modification and weight loss.

    • Jaclyn Sceneay
    •  & Sandra S. McAllister
  • News and Views |

    The lung undergoes a striking repair process in response to severe injuries such as influenza infection. A study now demonstrates that associated stem/progenitor cells are heterogeneous in nature and comprise subpopulations dominated by hypoxia/Notch or Wnt signalling. Modulation of this heterogeneity in favour of functional repair may have therapeutic value.

    • Jichao Chen
  • News and Views |

    The endosomal sorting complex required for transport (ESCRT)-III is critical for membrane abscission; however, the mechanism underlying ESCRT-III-mediated membrane constriction remains elusive. A study of the dynamic assembly and disassembly of the ESCRT-III machinery in vitro and in vivo now suggests that the turnover of the observed spiralling filaments is critical for membrane abscission during cytokinesis.

    • Henri G. Franquelim
    •  & Petra Schwille
  • News and Views |

    The mechanism of action of oncogenes in acute myeloid leukaemia is poorly understood. A study now shows that the fusion oncoprotein AML1-ETO regulates leukaemogenesis by increasing the expression of small nucleolar RNAs through post-transcriptional mechanisms, resulting in increased ribosomal RNA methylation, protein translation, and promotion of leukaemic-cell self-renewal and growth.

    • Mona Khalaj
    •  & Christopher Y. Park
  • News and Views |

    Haem is an iron-containing cofactor required for life. Many cellular processes rely on haem and failure to maintain iron homeostasis results in numerous pathological conditions. A study now identifies a Caenorhabditis elegans inter-organ signalling pathway in which secreted intestinal HRG-7 and neuronally secreted BMP signals coordinate animal haem homeostasis.

    • Jason N. Pitt
    •  & Matt Kaeberlein
  • News and Views |

    Several markers of gastric stem cells have been identified in recent years. Now a study demonstrates that Lgr5 marks a population of reserve stem cells located at the base of the corpus glands of the gastric epithelium, and that these cells can also act as a cell-of-origin for gastric tumorigenesis.

    • Toby J. Phesse
    •  & Owen J. Sansom
  • News and Views |

    Fusion between the inner membranes of two mitochondria requires the GTPase optic atrophy 1 (OPA1), but the molecular mechanism is poorly understood. A study now shows that fusion of two liposomes can be performed by OPA1 tethered to just one liposome, through an interaction with the phospholipid cardiolipin on the opposing liposome.

    • Raymond Liu
    •  & David C. Chan