Cell biology

  • Article
    | Open Access

    The formation of a hollow lumen surrounded by cells is a key developmental process that sets the shape of tissues and organs. Here, the authors show how the combined influence of geometric constraints imposed by cell packing and osmotic pressure can generate the diverse range in lumen shapes observed in different tissues.

    • Claudia G. Vasquez
    • , Vipul T. Vachharajani
    •  & Alexander R. Dunn
  • Article
    | Open Access

    Anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma often with poor prognosis. To identify genes defining ALCL cell state and dependencies, the authors here characterize ALCL-specific super-enhancers and describe the BATF3/IL-2R−module as a therapeutic opportunity for ALCL.

    • Huan-Chang Liang
    • , Mariantonia Costanza
    •  & Olaf Merkel
  • Article
    | Open Access

    The mechanisms that allow cancer cells to survive with monosomies are poorly understood. Here the authors analyse p53-deficient monosomic cell lines using transcriptomics and proteomics, and find that impaired ribosome biogenesis and p53 downregulation are associated with sustained monosomies.

    • Narendra Kumar Chunduri
    • , Paul Menges
    •  & Zuzana Storchova
  • Article
    | Open Access

    Human early development remains largely inaccessible, owing to technical and ethical limitations of working with natural embryos. Here the authors assess the extent to which human expanded pluripotent stem cells can specify distinct cell lineages and capture aspects of early human embryogenesis.

    • Berna Sozen
    • , Victoria Jorgensen
    •  & Magdalena Zernicka-Goetz
  • Article
    | Open Access

    Actin-based structures in cells and tissues are built and maintained through a poorly understood balance between assembly and disassembly. Here, our findings provide insights into how factors known to promote these opposing effects dynamically integrate to shape cells and tissue systems.

    • Elena E. Grintsevich
    • , Giasuddin Ahmed
    •  & Jonathan R. Terman
  • Article
    | Open Access

    Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

    • Emilie Crouchet
    • , Simonetta Bandiera
    •  & Thomas F. Baumert
  • Article
    | Open Access

    Ribonucleoprotein (RNP) granules are responsible for mRNA transport and local translation required for neuronal and oocyte maturation. Here the authors show that loss of the Drosophila Ub ligase Hecw enlarges RNP granules, leads to a liquid to gel-like transition, and results in defective oogenesis and neuronal loss.

    • Valentina Fajner
    • , Fabio Giavazzi
    •  & Simona Polo
  • Article
    | Open Access

    The authors show that post-transcriptional regulation of the cilia-driven leftward flow target dand5 is central to symmetry breakage in frog, fish and mouse and is mediated by a 139 nt Bicc1 responsive element in the dand5 3′UTR, and they present evidence that Pkd2 regulates this Bicc1/dand5 module.

    • Markus Maerker
    • , Maike Getwan
    •  & Axel Schweickert
  • Article
    | Open Access

    DNA:RNA hybrids (R-loops) are products of transcription that impact genome integrity and gene expression. Here the authors reveal a mechanism for regulating R-loops in a ubiquitination-dependent manner controlled by the activities of USP11 and KEAP1

    • Mateusz Jurga
    • , Arwa A. Abugable
    •  & Sherif F. El-Khamisy
  • Article
    | Open Access

    p53 isoform Δ133p53β is reported to promote intrinsic oncogenic functions. Here the authors show Δ133p53β is sequestered as aggregates in an inactive form, while association with interacting partners including p63 isoforms and the CCT chaperone complex promotes Δ133p53β activity, resulting in enhanced cancer cell migration and invasion.

    • Nikola Arsic
    • , Tania Slatter
    •  & Pierre Roux
  • Article
    | Open Access

    Molecular tethers physically bridge transport vesicles to their target membranes as a prerequisite step for fusion. Here the authors control vesicle tethering using optogenetic approaches to study the interplay between vesicle tethering and fusion.

    • Seong J. An
    • , Felix Rivera-Molina
    •  & Derek Toomre
  • Article
    | Open Access

    MAD2L2 — a member of the shieldin complex — is known to play important roles in DNA repair. Here the authors demonstrate how MAD2L2 dimerization mediated through SHLD2 participates in shieldin assembly and function.

    • Inge de Krijger
    • , Bastian Föhr
    •  & Jacqueline J. L. Jacobs
  • Article
    | Open Access

    It is unclear how bacterial cells adapt the reversible switching of flagellar motor rotation to environments of different viscosities. Here, Antani et al. show that flagellar mechanosensors allosterically control the motor’s binding affinity for the chemotaxis response regulator, CheY-P, to adapt flagellar switching over varying viscous loads.

    • Jyot D. Antani
    • , Rachit Gupta
    •  & Pushkar P. Lele
  • Article
    | Open Access

    During herpesvirus infection, most individuals intrinsically suppress a primary infection and therewith preclude potential damage or neurodegeneration of the CNS. Here, Ames et al. show that Optineurin (OPTN), a conserved autophagy receptor, restricts HSV-1 spread, degrades viral VP16 through autophagy and is neuroprotective against HSV infection in vivo.

    • Joshua Ames
    • , Tejabhiram Yadavalli
    •  & Deepak Shukla
  • Article
    | Open Access

    Transport protein particle (TRAPP) is a multimeric protein complex regulating membrane trafficking pathways. Here the authors show that TRAPPC4, a core subunit of TRAPP complex, is required for RAB11-mediated recycling of PD-L1, affecting T-cell-mediated anti-tumor immune responses.

    • Yimeng Ren
    • , Yun Qian
    •  & Jing-Yuan Fang
  • Article
    | Open Access

    Met1-linked linear ubiquitination (M1-Ubi) is catalyzed by linear ubiquitin chain assembly complex (LUBAC). Here the authors show that Ago2 protein is M1-Ubi modified by LUBAC complex under hypoxia condition leading to less association of miRNA target mRNAs to Ago2 protein and de-repression of miRNA targets.

    • Hailong Zhang
    • , Xian Zhao
    •  & Jianxiu Yu
  • Article
    | Open Access

    Dynamin mediates the fission of vesicles during endocytosis. Here, the authors report the cryoEM structure of a super-constricted two-start dynamin 1 filament- one of the two known helical forms of dynamin, with insights into the molecular mechanisms of dynamin-mediated membrane scission.

    • Jiwei Liu
    • , Frances Joan D. Alvarez
    •  & Peijun Zhang
  • Article
    | Open Access

    Epigenetic changes are implicated in Acute myeloid leukemia (AML) tumorigenesis. Here, the authors show that the ubiquitin ligase RNF5 and its substrate RBBP4 contribute to AML development by regulating epigenetic-controlled transcription which determines AML sensitivity to HDAC inhibitors.

    • Ali Khateb
    • , Anagha Deshpande
    •  & Ze’ev A. Ronai
  • Article
    | Open Access

    The large and small subunits of the ribosome are synthesized independently within the nucleolus — a membrane-less compartment within the nucleus — before being exported into the cytoplasm. Here, the authors use in situ cryo-ET to observe ribosome maturation and reveal the native organization of the nucleolus.

    • Philipp S. Erdmann
    • , Zhen Hou
    •  & Wolfgang Baumeister
  • Article
    | Open Access

    The assembly of branched actin networks depends on the heterodimeric capping protein CP/CapZ. Combining cryoEM, in vitro reconstitution and cell biological assays, the authors show that CP not only prevents actin filament elongation but also selectively masks actin filament ends to promote nucleation.

    • Johanna Funk
    • , Felipe Merino
    •  & Peter Bieling
  • Article
    | Open Access

    The Spike protein of SARS-CoV-2 has a C-terminal cytoplasmic tail. Here the authors show that this tail binds trafficking machinery via sequences that appear optimised to ensure that Spike accumulates at the site of viral budding in the Golgi but that some can also traffic to the cell surface to induce syncytia formation.

    • Jérôme Cattin-Ortolá
    • , Lawrence G. Welch
    •  & Sean Munro
  • Article
    | Open Access

    The mechanisms underlying the activity of non-receptor tyrosine kinase, TNK1, in cancers are unclear. Here the authors show that MARK mediates 14-3-3 and TNK1 interaction which restrains TNK1 activity, while the release of TNK1 from 14-3-3 leads to TNK1 activation through its interaction with ubiquitin and thus results in TNK1-mediated tumor growth in vivo

    • Tsz-Yin Chan
    • , Christina M. Egbert
    •  & Joshua L. Andersen
  • Article
    | Open Access

    PAK4 is a kinase involved in cell-cell junctions, though the identify of the  local protein network involving PAK4 is unclear. Here, the authors performed proximity proteomic analysis on mammalian PAK4 and find  that PAK4 is associated with Afadin-dependent junctions, and report putative PAK4 phosphorylation substrates at this site.

    • Yohendran Baskaran
    • , Felicia Pei-Ling Tay
    •  & Edward Manser
  • Article
    | Open Access

    Tissue circadian clocks contribute to the regulation of physiology and metabolism. Here the authors investigate the role of the intestinal circadian clock in energy homeostasis and show that the intestinal clock acts as an accelerator in dietary fat absorption.

    • Fangjun Yu
    • , Zhigang Wang
    •  & Baojian Wu
  • Article
    | Open Access

    The unfolded protein response (UPR) promotes cell survival in cancers with hyperactive ER stress response. Here the authors show that CARM1, an arginine methyltransferase, controls the IRE1α/XBP1 pathway of the UPR and the inhibition of this pathway can inhibit growth in CARM1 expressing ovarian cancers.

    • Jianhuang Lin
    • , Heng Liu
    •  & Rugang Zhang
  • Article
    | Open Access

    Humans and other large mammals heal wounds by forming fibrotic scar tissue with diminished function. Here, the authors show that disrupting mechanotransduction through the focal adhesion kinase pathway in large animals accelerates healing, prevents fibrosis, and enhances skin regeneration.

    • Kellen Chen
    • , Sun Hyung Kwon
    •  & Geoffrey C. Gurtner
  • Article
    | Open Access

    Cell death is a critical process in health and disease, yet available markers record later stages of cell death once a cell has already begun to decompose. Here the authors show the use of a genetically encoded calcium indicator that demarcates an irreversible stage of cell death earlier than previously possible.

    • Jeremy W. Linsley
    • , Kevan Shah
    •  & Steven Finkbeiner
  • Article
    | Open Access

    β-actin loss can affect gene expression and heterochromatin organization. Here the authors conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) to investigate the impact of changes in β-actin levels on 3d genome architecture and chromatin remodeling activities of BAF and polycomb proteins.

    • Syed Raza Mahmood
    • , Xin Xie
    •  & Piergiorgio Percipalle
  • Article
    | Open Access

    Streptomyces bacteria have a linear chromosome and a complex life cycle, including development of multi-genomic hyphae that differentiate into mono-genomic exospores. Here, Szafran et al. show that the chromosome of Streptomyces venezuelae undergoes substantial remodelling during sporulation, from an ‘open’ to a ‘closed’ conformation.

    • Marcin J. Szafran
    • , Tomasz Małecki
    •  & Dagmara Jakimowicz
  • Article
    | Open Access

    Misfolded proteins are ubquitinated and subsequently condensed by cargo receptors for selective autophagy. Here, the authors use in vitro reconstitution to elegantly dissect how the receptors p62/SQSTM1, NBR1 and TAX1BP1 contribute to p62-ubiquitin condensate formation and degradation by autophagy.

    • Eleonora Turco
    • , Adriana Savova
    •  & Sascha Martens
  • Article
    | Open Access

    Streptomyces bacteria have a linear chromosome, with core genes located in the central region and gene clusters for specialized metabolite biosynthesis found in the ‘arms’. Here, Lioy et al. show that such chromosome structure correlates with genetic compartmentalization, and the onset of metabolic differentiation is accompanied by a rearrangement of chromosome architecture.

    • Virginia S. Lioy
    • , Jean-Noël Lorenzi
    •  & Stéphanie Bury-Moné
  • Article
    | Open Access

    Higher-order chromatin structure is temporarily disrupted during mitosis. Here the authors show that loss of the architectural factor CTCF results in failure to form structural loops and leads to inappropriate cis-regulatory contacts and alterations of compartmental interactions after mitosis. Furthermore, they show global 3D architecture is set up without transcription, but that transcription contributes to proper gene domain formation.

    • Haoyue Zhang
    • , Jessica Lam
    •  & Gerd A. Blobel
  • Article
    | Open Access

    Cells in the developing embryo interpret WNT signalling with context-dependence, but the mechanism decoding these cues is unclear. Here, the authors show that combinatorial TALE/HOX activity destabilizes nucleosomes at WNT-responsive regions to activate paraxial mesodermal genes.

    • Luca Mariani
    • , Xiaogang Guo
    •  & Elisabetta Ferretti
  • Article
    | Open Access

    High cholesterol has been associated with increased risk of cancer but the underlying mechanism is not completely understood. Here, the authors show that a cholesterol metabolite induces metabolic reprogramming that generates ferroptosis-resistant cancer cells leading to increased tumour growth and metastasis.

    • Wen Liu
    • , Binita Chakraborty
    •  & Donald P. McDonnell
  • Article
    | Open Access

    The membrane lipids change with ageing and function as regulatory molecules, but the underlying mechanisms are incompletely understood. Here, the authors identify C22 glucosylceramide as a regulator of the longevity transcription factor SKN-1, and show that C22 glucosylceramide regulates lifespan by controlling lysosome homeostasis and subsequent TOR activation.

    • Feng Wang
    • , Yuxi Dai
    •  & Shanshan Pang
  • Article
    | Open Access

    Cholesterol metabolism is involved in the progression of aggressive prostate cancer (PCa). Here the authors show that miR-205 downregulation promotes cholesterol synthesis and androgen receptor signalling in PCa through enhancing the expression of the rate-limiting enzyme of cholesterol synthesis, squalene epoxidase.

    • C. Kalogirou
    • , J. Linxweiler
    •  & A. Schulze
  • Article
    | Open Access

    Sumoylation is important for the assembly and function of the SMN complex, which plays a central role in RNA processing. Here the authors show that loss of this posttranslational modification impairs the ability of SMN to correct selective deficits in the sensory-motor circuit of animal models of spinal muscular atrophy.

    • Giulietta M. Riboldi
    • , Irene Faravelli
    •  & Francesco Lotti
  • Article
    | Open Access

    Skeletal muscle stem cells (or satellite cells, SCs) are normally quiescent but activate and expand in response to injury. Here the authors show that induction of DHX36 helicase during SC activation promotes mRNA translation by binding to 5′UTR mRNA G-quadruplexes (rG4) in targets including Gnai2 and unwinding them.

    • Xiaona Chen
    • , Jie Yuan
    •  & Huating Wang
  • Article
    | Open Access

    The BRCA1-PALB2-BRCA2-RAD51 (BRCA1-P) complex is well known to play a fundamental role in DNA repair, but how the complex recruitment is regulated is still a matter of interest. Here the authors reveal mechanistic insights into RNF168 activity being responsible for PALB2 recruitment, through BARD1-BRCA1 during homologous recombination repair.

    • John J. Krais
    • , Yifan Wang
    •  & Neil Johnson