Reviews & Analysis

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  • The heart is a complex organ, consisting of multiple cell types that coordinately regulate blood flow. Reciprocal Notch pathway signalling in endocardial and myocardial cells is now shown to promote maturation of the ventricular chambers. These insights reveal mechanisms that, when disrupted, can lead to cardiomyopathies.

    • Casey A. Gifford
    • Deepak Srivastava
    News & Views
  • The heptameric Arp2/3 complex generates branched actin filament networks that drive lamellipodium protrusion, vesicle trafficking and pathogen motility. Distinct variants of the Arp2/3 complex are now shown to have different roles in tuning actin assembly and disassembly, in concert with the prominent actin regulators cortactin and coronin.

    • Klemens Rottner
    • Theresia E. B. Stradal
    News & Views
  • Spatiotemporally distinct pluripotent states captured in vitro provide an accessible way of modelling early human development. An intricate interplay between the metabolome and histone modifications is now shown to drive the metabolic switch from human naive to primed pluripotency, one of the earliest steps of embryogenesis.

    • Jun Wu
    • Juan Carlos Izpisua Belmonte
    News & Views
  • A powerful combination of two-colour imaging in vivo, Fourier-filtered kymography and simulations provides a high-resolution view of kinesin-2 transport dynamics in cilia. This study reveals heterotrimeric kinesin-II as an 'obstacle-course runner' and homodimeric OSM-3 (KIF17) as a 'long-distance runner', and elucidates the 'baton handoff' between these two kinesin-2 motors on the microtubule track.

    • Robert O'Hagan
    • Maureen M. Barr
    News & Views
  • Tumours reprogram their metabolism to maximize macromolecule biosynthesis for growth. However, which of the common tumour-associated metabolic activities are critical for proliferation remains unclear. Glutamate-derived glutamine is now shown to satisfy the glutamine needs of glioblastoma, indicating that glutamine anaplerosis is dispensable for growth.

    • Abigail S. Krall
    • Heather R. Christofk
    News & Views
  • The mechanisms underlying integrin-dependent signalling are a topic of continued study. Endocytosed integrins are now shown to drive assembly of signalling complexes on the cytoplasmic face of endocytic membranes to promote cancer cell survival and increase metastatic capacity following cell detachment.

    • Elena Rainero
    • Jim C. Norman
    News & Views
  • Two studies show that the E3 ubiquitin ligase RNF138 is recruited to DNA double-strand break sites, where it ubiquitylates key repair factors to promote DNA-end resection and homologous recombination. These findings add insights into the multilayered regulatory mechanisms underlying DNA double-strand break repair pathway choice in mammalian cells.

    • Simon Bekker-Jensen
    • Niels Mailand
    News & Views
  • Protein ubiquitylation in mammals is known to trigger selective autophagy of peroxisomes through a process termed pexophagy. The physiological peroxisomal target for pexophagy-related ubiquitylation has been controversial, but two studies have now identified the protein PEX5 as the real candidate.

    • Suresh Subramani
    News & Views
  • Cellular senescence is often accompanied by the production of secreted proteins that mediate the diverse effects of senescence on the tissue microenvironment. The mammalian target of rapamycin (mTOR), a master regulator of protein synthesis, is now shown to control the senescence-associated secretory phenotype by modulating gene transcription and mRNA translation and stabilization.

    • Kosuke Tomimatsu
    • Masashi Narita
    News & Views
  • Decreases in endoplasmic reticulum calcium content are sensed by resident STIM proteins, which can activate plasma membrane Orai channels to facilitate Ca2+ entry. The role of STIMATE, a previously unknown component of the store-operated calcium entry complex, has now been identified and defined.

    • Robert Hooper
    • Jonathan Soboloff
    News & Views
  • Compared with most intracellular vesicles, the autophagosome is formed by an unusual event of vesicle budding involving an elusive sequence of membrane expansions that ends with a double membrane vesicle. It is now shown that actin polymerization inside the forming autophagosome is a driving force for the expansion and assembly of a functional autophagosome.

    • Petter Holland
    • Anne Simonsen
    News & Views
  • A new study suggests that fumarase, a metabolic enzyme normally associated with ATP production in mitochondria, is recruited to sites of DNA damage where it produces fumarate to inhibit histone demethylation and promote repair of DNA double strand breaks.

    • Susan P. Lees-Miller
    News & Views
  • Microtubule polymerization is initiated by γ-tubulin containing complexes. Petry and Vale discuss factors involved in localizing and activating γ-tubulin at different locations in the cell.

    • Sabine Petry
    • Ronald D. Vale
    Perspective
  • Modelling organs in culture has great potential to improve our understanding of development, organogenesis and disease. While some endodermal derived organs have been modelled, the corpus region of the stomach, where acid-producing cells reside, remained an invincible target. A 60-day differentiation protocol now enables the generation of functional acid-producing cells in culture, conquering the challenge.

    • Meritxell Huch
    News & Views
  • Activator E2Fs and Myc cooperate as master regulators of proliferation. A new study sheds light on one of the fundamental questions in cancer biology: how do oncogenic changes, such as Retinoblastoma (RB)-mutation, modify E2F and Myc activity?

    • Wayne O. Miles
    • Nicholas J. Dyson
    News & Views
  • Mitotic chromosome condensation has fascinated biologists since Flemming's early illustrations of mitosis in the late nineteenth century. Now — 130 years later — chromatid condensation is reconstituted in vitro with the minimum components. The results are remarkably and beautifully simple, requiring only core histones, three histone chaperones, topoisomerase II and condensin I.

    • Jason C. Bell
    • Aaron F. Straight
    News & Views
  • Integrin-based focal adhesions integrate biochemical and biomechanical signals from the extracellular matrix and the actin cytoskeleton. The combination of three-dimensional super-resolution imaging and loss- or gain-of-function protein mutants now links the nanoscale dynamic localization of proteins to their activation and function within focal adhesions.

    • Grégory Giannone
    News & Views
  • The eukaryotic cell uses two complex machineries to degrade unwanted proteins. The first is the ubiquitin–proteasome system and the second is autophagy. A new study contributes to our understanding of how the two systems interconnect to coordinate protein degradation.

    • Sascha Martens
    • Andreas Bachmair
    News & Views
  • Phagocytic cells engulf their prey into vesicular structures called phagosomes, of which a certain proportion becomes demarcated for enhanced maturation by a process called LC3-associated phagocytosis (LAP). Light has now been shed on the molecular requirements of LAP, establishing a central role for the protein Rubicon in the immune response to Aspergillus fumigatus.

    • Keith B. Boyle
    • Felix Randow
    News & Views