Cell biology

  • Article
    | Open Access

    It is increasingly recognised that the spatial localisation of RNA is important for proper cellular function. Here, the authors investigate RNA localisation in skeletal muscle and develop methods to show that global active transport of RNA is required to maintain dispersion of gene products in the large muscle syncytium.

    • Lance T. Denes
    • , Chase P. Kelley
    •  & Eric T. Wang
  • Article
    | Open Access

    Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) is normally induced by innate immunity sensing for protection from pathogens. Here the authors show that cGAMP is also upstream of DNA damage signaling by activating ATM-CHK2-mediated repair pathway, while simultaneously suppressing the homology-directed repair.

    • Daipayan Banerjee
    • , Kurt Langberg
    •  & Nagaraj Kerur
  • Article
    | Open Access

    The centriole exhibits an evolutionarily conserved 9-fold radial symmetry that stems from a cartwheel containing vertically stacked ring polymers that harbor 9 homodimers of the protein SAS-6. Here the authors show how dual properties inherent to surface-guided SAS-6 self-assembly possess spatial information that dictates correct scaffolding of centriole architecture.

    • Niccolò Banterle
    • , Adrian P. Nievergelt
    •  & Pierre Gönczy
  • Article
    | Open Access

    Cancer cells in culture are often grown in media conditions containing unphysiological metabolite levels. Here, the authors grow cells under physiological metabolite levels to further understand the reliance of cells on serine and find that when grown under these conditions the cells are less sensitive to serine withdrawal.

    • Marc Hennequart
    • , Christiaan F. Labuschagne
    •  & Karen H. Vousden
  • Article
    | Open Access

    Chronic desynchronization between physiological and behavioral rhythms has been linked to the onset of metabolic diseases. Here the authors control the cyclic metabolic signals in a microfluidic device to study the effects of the timing, period and frequency of glucose and insulin on the transcriptome of cultured fibroblasts.

    • Onelia Gagliano
    • , Camilla Luni
    •  & Nicola Elvassore
  • Article
    | Open Access

    The 20S particle is part of the 26S proteasome, but also exists as a free complex. Here, the authors outline signature activities of the 20S and combine chemical, structural, functional and proteomic assays to show that the 20S can degrade ubiquitin tags along with conjugated substrates.

    • Indrajit Sahu
    • , Sachitanand M. Mali
    •  & Michael H. Glickman
  • Article
    | Open Access

    RIPK1 is critical for normal development and cell death. Here, the authors identify a metabolic role for RIPK1 in aspartate homeostasis, as increased aspartate levels in RIPK1-deficient cells inhibits starvation-induced autophagy by ULK1.

    • Xinyu Mei
    • , Yuan Guo
    •  & Zheng-Jiang Zhu
  • Article
    | Open Access

    Macrophage inflammation promotes insulin resistance during diet-induced obesity. Here the authors show that macrophage NOC4L is decreased in humans and mice with obesity, that macrophage NOC4L deficiency aggravated high-fat diet induced inflammation and insulin resistance, and that NOC4L interacts with toll-like receptor 4, to inhibit endocytosis, and thus blocks TLF4/TRIF inflammatory signaling.

    • Yongli Qin
    • , Lina Jia
    •  & Xiangdong Li
  • Article
    | Open Access

    The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy remain elusive. Here the authors use an siRNA library to screen lipid-binding proteins, and identify the kinases GAK and PRKCD as positive regulators of PRKN-independent mitophagy.

    • Michael J. Munson
    • , Benan J. Mathai
    •  & Anne Simonsen
  • Article
    | Open Access

    Changes in intracellular GTP levels are not considered as a regulatory event in RAC1 activation in live cells since total GTP levels are substantially higher than the RAC1 GTP dissociation constant determined in vitro. Here, the authors demonstrate that the availability of free GTP in live cells controls the activity of RAC1 and cell invasion.

    • Anna Bianchi-Smiraglia
    • , David W. Wolff
    •  & Mikhail A. Nikiforov
  • Article
    | Open Access

    Pathologic protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells via extracellular vesicles or direct cell-to-cell contact. Here, Liu et al. show that viral glycoproteins can contribute to intercellular proteopathic seed transmission via both routes.

    • Shu Liu
    • , André Hossinger
    •  & Ina M. Vorberg
  • Article
    | Open Access

    Cellular membranes have distinct lipid compositions despite intermixing, and it is unclear why plasma membrane lipids do not accumulate on endosomes. Here, the authors use the C. elegans embryo to identify lipid transfer proteins and phosphatases that are critical for endosomal lipid homeostasis.

    • Darshini Jeyasimman
    • , Bilge Ercan
    •  & Yasunori Saheki
  • Article
    | Open Access

    Calcineurin — the Ca2+ regulated phosphatase and target of immunosuppressants — regulates GPCR-mediated phospholipid signaling at the plasma membrane. Here the authors show that CNAβ1 (a poorly studied isoform of the calcineurin catalytic subunit) is targeted to the plasma membrane through palmitoylation to dephosphorylate and promote PI4KA complex activity.

    • Idil Ulengin-Talkish
    • , Matthew A. H. Parson
    •  & Martha S. Cyert
  • Article
    | Open Access

    Tumor necrosis factor (TNF) has various effects on phosphorylation-mediated cellular signaling. Combining phosphoproteomics, subcellular localization analyses and kinase inhibitor assays, the authors provide systems level insights into TNF signaling and identify modulators of TNF-induced cell death.

    • Maria C. Tanzer
    • , Isabell Bludau
    •  & Matthias Mann
  • Article
    | Open Access

    The γ-tubulin ring complex (γTuRC) nucleates microtubules at the centrosome, but how this function is related to γTuRC subcentrosomal distribution is unclear. Here the authors show that γTuRC in the centriole lumen has a nucleation-independent role in centriole integrity and cilium assembly.

    • Nina Schweizer
    • , Laurence Haren
    •  & Jens Lüders
  • Article
    | Open Access

    Osmotic compensation by electroneutral ion transport buffers TORC1-mediated changes in the cytosolic proteome, and maintains intracellular homeostasis and cell volume over the circadian cycle. Here, the authors find such ion content changes drive daily rhythms in cardiomyocyte electrical activity.

    • Alessandra Stangherlin
    • , Joseph L. Watson
    •  & John S. O’Neill
  • Article
    | Open Access

    Biomechanical mechanisms orchestrating stem cell dynamics in development remain unclear. Here the authors show that guidance receptor Plexin-B2 organizes actomyosin contractility, cytoskeletal tension and adhesion during multicellular development of human embryonic stem cells and neuroprogenitor cells.

    • Chrystian Junqueira Alves
    • , Rafael Dariolli
    •  & Roland H. Friedel
  • Article
    | Open Access

    The immune response to herpes simplex virus is essential in limiting immunopathology during infection, however factors linked to neuroprotection are currently unclear. Here the authors implicate mTORC2 in the host response to viral infection and link to neuroprotection.

    • Rahul K. Suryawanshi
    • , Chandrashekhar D. Patil
    •  & Deepak Shukla
  • Article
    | Open Access

    The connection between cell cycle, metabolic state and mitochondrial activity is unclear. Here, the authors show that p107 represses mitochondrial transcription and ATP output in response to glycolytic byproducts, causing metabolic control of the cell cycle rate in myogenic progenitors.

    • Debasmita Bhattacharya
    • , Vicky Shah
    •  & Anthony Scimè
  • Article
    | Open Access

    How phase separation participates in mitophagy remains unclear. Here the authors show that Nur77 and p62/SQSTM1 through “head-to-head” and “tail-to-tail” interactions form membraneless condensates capable of sequestering dysfunctional mitochondria and tethering them to autolysosome for degradation.

    • Shuang-zhou Peng
    • , Xiao-hui Chen
    •  & Xiao-kun Zhang
  • Article
    | Open Access

    Changes in cell mechanics contribute to cancer cell dissemination. Here the authors show that high plasma membrane (PM) tension inhibits cancer dissemination by counteracting mechanosensitive BAR family protein assembly, while restoration of PM tension phenotypically convert malignant cells into a non-motile epithelial cell state.

    • Kazuya Tsujita
    • , Reiko Satow
    •  & Toshiki Itoh
  • Article
    | Open Access

    Aberrant EGFR activation is commonly found in non-small cell lung cancer (NSCLC). Here the authors show that E3 ubiquitin ligase FBXL2 targets EGFR and EGFR tyrosine kinase inhibitor (TKI)-resistant mutants for proteasome-mediated degradation to inhibit EGFR-driven NSCLC growth and TKI resistance.

    • Mengmeng Niu
    • , Jing Xu
    •  & Zhi-Xiong Jim Xiao
  • Article
    | Open Access

    OTULIN is a deubiquitinase for linear ubiquitin chains. Here the authors show, using genetic mouse models and single-cell RNA-sequencing, that deficiency of OTULIN in keratinocytes causes skin inflammation and verrucous carcinoma via the induction of keratinocyte death, thereby implicating a function of OTULIN in keratinocyte homeostasis.

    • Esther Hoste
    • , Kim Lecomte
    •  & Geert van Loo
  • Article
    | Open Access

    OTULIN is a negative regulator of linear ubiquitination, and its deficiency in human causes multi-organ inflammations including the skin. Here the authors show, by combining various genetic tools with epidermis-specific Otulin knockout mice, that Otulin suppresses skin inflammation predominantly by inhibiting RIPK1-mediated keratinocytes necroptosis.

    • Hannah Schünke
    • , Ulrike Göbel
    •  & Manolis Pasparakis
  • Article
    | Open Access

    Lipid droplet biogenesis is orchestrated by the conserved membrane protein Seipin via an unknown mechanism. Here, the authors use structural, biochemical and molecular dynamics simulation approaches to reveal the mechanism of lipid droplet formation by the yeast Seipin Sei1 and its partner Ldb16.

    • Yoel A. Klug
    • , Justin C. Deme
    •  & Pedro Carvalho
  • Article
    | Open Access

    During meiosis, chromosomes undergo dramatic changes in morphology and intranuclear positioning. Here the authors mapped the 3D genome architecture throughout mouse spermatogenesis by Hi-C of sorted cells to reveal the contributions of transcriptional activity and mechanical force in modulating homolog alignment and recombination.

    • Wu Zuo
    • , Guangming Chen
    •  & Qian Bian
  • Article
    | Open Access

    Cilia, tiny outgrowths of cells, are essential for life. Here, the author’s describe the scaffold protein TRIP6, which promotes the assembly of ciliary proteins required for ciliogenesis, and show that its absence results in hydrocephalus.

    • Shalmali Shukla
    • , Ronny Haenold
    •  & Peter Herrlich
  • Article
    | Open Access

    Phase separation has been suggested as a mechanism for heterochromatin formation through condensation of heterochromatin-associated factors. Here the authors show Polycomb complex PRC1 forms condensates on chromatin. Using optogenetic tools they nucleate local Polycomb condensates to show that this phase separation leads to subsequent histone modifications and chromatin compaction.

    • Jorine M. Eeftens
    • , Manya Kapoor
    •  & Clifford P. Brangwynne
  • Article
    | Open Access

    Microtubule tracks are important for the transport of molecules within axons. Here, the authors show that ATAT1, the enzyme responsible for acetylating a-tubulin, receives acetyl groups from ATP citrate lyase whose stability is regulated by Elongator, a protein mutated in the neuronal disease Familial dysautonomia.

    • Aviel Even
    • , Giovanni Morelli
    •  & Laurent Nguyen
  • Article
    | Open Access

    The glucose transporter GLUT1 is upregulated in multiple cancers and may contribute to tumour progression, but the underlying mechanisms are poorly understood. Here, the authors show that DHHC9-mediated GLUT1 palmitoylation at Cys207 is crucial for plasma membrane localisation of GLUT1 and for tumourigenesis in glioblastoma cells.

    • Zhenxing Zhang
    • , Xin Li
    •  & Xinjian Li
  • Article
    | Open Access

    Proliferative and effector functions of T cells are determined by T cell receptor signalling and modulated by activator and inhibitory co-receptors. Authors report here that the G-protein-coupled receptor GPR171 functions as a co-inhibitor of T cell signalling and might serve as a target for cancer immunotherapy.

    • Yuki Fujiwara
    • , Robert J. Torphy
    •  & Yuwen Zhu
  • Article
    | Open Access

    Ciliary beating is mediated by the axonemal central pair microtubules, though how these non-centrosomal microtubules form is poorly understood. Here the authors show that a trio of proteins act cooperatively to initiate central microtubule formation in mammals.

    • Hao Liu
    • , Jianqun Zheng
    •  & Xiumin Yan
  • Article
    | Open Access

    Two-pore channels (TPCs) are cation channels that localize to acidic organelles to regulate Ca2+ dependent events. Here, Li et al. characterize a TPC from Toxoplasma gondii(TgTPC) that localizes to the apicoplast, is critical for maintaining its integrity and relevant for Ca2+ uptake from the ER through stabilizing inter-organelle contact.

    • Zhu-Hong Li
    • , Thayer P. King
    •  & Silvia N. J. Moreno
  • Article
    | Open Access

    The TOM and TIM23 complexes facilitate the transport of nuclear-encoded proteins into the mitochondrial matrix. Here, the authors use a stalled client protein to purify the translocation supercomplex and gain insight into the TOM-TIM23 interface and the mechanism of protein handover from the TOM to the TIM23 complex.

    • Ridhima Gomkale
    • , Andreas Linden
    •  & Peter Rehling
  • Article
    | Open Access

    Cell migration is essential for many physiological processes. Its deregulation causes cancer metastasis and it is not well understood how it is tightly controlled. We identify NHSL1 as a negative regulator of actin nucleating Scar/WAVE-Arp2/3 complexes, cell protrusion stability, and cell migration.

    • Ah-Lai Law
    • , Shamsinar Jalal
    •  & Matthias Krause
  • Article
    | Open Access

    Mutations within subunits of the tRNA splicing endonuclease complex (TSEN) are associated with pontocerebellar hypoplasia (PCH). Here the authors show that tRNA intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers, and provide evidence that modulation of TSEN stability may contribute to PCH phenotypes.

    • Samoil Sekulovski
    • , Pascal Devant
    •  & Simon Trowitzsch
  • Article
    | Open Access

    Several bacteria in the gut microbiota have been associated with colorectal cancer (CRC) but it is not completely clear whether they have a role in tumourigenesis. Here, the authors show enrichment of 12 bacterial taxa in two cohorts of CRC patients and that two Porphyromonas species accelerate CRC onset through butyrate secretion.

    • Shintaro Okumura
    • , Yusuke Konishi
    •  & Eiji Hara
  • Article
    | Open Access

    Extracellular vesicles (EV) are known to be released from the primary cilium, but the role ciliary proteins play in EV biogenesis remains unexplored. Here, the authors demonstrate increased secretion of small EVs with altered cargo composition from cells with known ciliarelated mutations. Wnt related molecules made up a majority of altered cargo

    • Ann-Kathrin Volz
    • , Alina Frei
    •  & Helen L. May-Simera