Cell biology articles within Nature Communications

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  • Article
    | Open Access

    There are two technical impediments for using purified Wnt proteins in serum-free stem cell cultures: rapid loss of activity and toxicity of detergents to stem cell self-renewal. Here, the authors show that lipid-stabilized Wnt3a can establish long-term culture of human intestinal and liver organoids.

    • Nesrin Tüysüz
    • , Louis van Bloois
    •  & Derk ten Berge
  • Article
    | Open Access

    Potassium channels are essential for modulating T-cell functions. Here, by characterizing rat models and analysing human T cells, the authors identify differential requirements of two potassium channel proteins, Kv1.3 and KCa3.1, for the induction of conventional versus autoreactive T-cell responses.

    • Eugene Y. Chiang
    • , Tianbo Li
    •  & Jane L. Grogan
  • Article
    | Open Access

    Gluconeogenesis is downregulated in hepatocellular carcinoma. Here, the authors show that nuclear receptor Nur77 acts as a tumour suppressor sustaining gluconeogenesis by enhancing phosphoenolpyruvate carboxykinase (PEPCK1) stability via regulating its interaction with the SUMO-conjugating enzyme Ubc9.

    • Xue-li Bian
    • , Hang-zi Chen
    •  & Qiao Wu
  • Article
    | Open Access

    Neuronal migration is vital for neuronal circuit morphogenesis and is thought to rely on microtubule-actomyosin crosstalk. Here, the authors use super-resolution imaging and the drebrin microtubule-actin crosslinking protein to show that microtubule-actomyosin coupling controls the direction of centrosome and somal motility.

    • Niraj Trivedi
    • , Daniel R. Stabley
    •  & David J. Solecki
  • Article
    | Open Access

    Cytokinetic abscission relies on the local constriction after cytoskeleton disassembly, but it is not known how the actin filaments are disassembled. Here, the authors show that the redox enzyme MICAL1 is recruited by Rab35 and induces oxidation-mediated depolymerization of actin, which is required to recruit ESCRT-III and complete abscission.

    • Stéphane Frémont
    • , Hussein Hammich
    •  & Arnaud Echard
  • Article
    | Open Access

    Cytoplasmic dynein 2 drives retrograde intraflagellar transport but little is known about its dynamics. Here the authors use fluorescence microscopy to track labelled dynein 2 inC. elegansat the single-molecule level and report diffusion at the ciliary base, and pausing and directional switches along the cilium.

    • Jona Mijalkovic
    • , Bram Prevo
    •  & Erwin J. G. Peterman
  • Article
    | Open Access

    Removal of senescent cells rejuvenates lungs of aged mice. Here the authors show that elimination of senescent cells using either genetic or pharmacological means improves lung function and physical health in a mouse model of idiopathic pulmonary fibrosis (IPF), suggesting potential therapy for treatment of human IPF.

    • Marissa J. Schafer
    • , Thomas A. White
    •  & Nathan K. LeBrasseur
  • Article
    | Open Access

    The translocon-associated protein complex (TRAP) is a crucial component of the endoplasmic reticulum protein translocon. Here the authors study native translocon structures from human disease patients and algae cells to determine the molecular organization of the TRAP complex.

    • Stefan Pfeffer
    • , Johanna Dudek
    •  & Friedrich Förster
  • Article
    | Open Access

    What keeps blood from clotting in homeostasis is a puzzle. Here, the authors suggest that lack of the enzyme disulfide isomerase (PDI) in the blood is key, and show that PDI is secreted only after vascular injury to act on substrates that include vitronectin, affecting its binding to αVβ3 and αIIbβ3 integrins and enabling thrombus formation.

    • Sheryl R. Bowley
    • , Chao Fang
    •  & Bruce Furie
  • Article
    | Open Access

    Proper heart development and synchronous cardiomyocyte contraction rely on tissue integrity. Here the authors show that the ubiquitin-proteasome system and the E3 ubiquitin ligase ASB2 in particular are crucial for cardiomyocyte maturation and tissue integrity through the degradation of the TCF3 transcription factor.

    • Ryuichi Fukuda
    • , Felix Gunawan
    •  & Didier Y. R. Stainier
  • Article
    | Open Access

    Mild heat stress has beneficial effects on organismal health and survival. Here, Kumstaet al. show that a mild heat shock and HSF-1 overexpression induce autophagy in multiple tissues of C. elegansand autophagy-related genes are essential for both heat shock-induced and HSF-1–mediated stress resistance and longevity.

    • Caroline Kumsta
    • , Jessica T. Chang
    •  & Malene Hansen
  • Article
    | Open Access

    Cancers accumulate multiple single copy number alterations, but their impact is unclear. Here, the authors computationally demonstrate a disruption of genes associated with autophagy in ovarian cancer, show impact on autophagic flux, and note the efficacy of autophagy drugs in preclinical models.

    • Joe Ryan Delaney
    • , Chandni B. Patel
    •  & Dwayne G. Stupack
  • Article
    | Open Access

    Usp9x is a deubiquitinating enzyme with altered expression in melanoma; however its functional contribution in this context is not clear. Here the authors show that Usp9x regulates the stability of the transcription factor Ets-1 that in turn impacts metastatic melanoma through increased expression of NRAS.

    • Harish Potu
    • , Luke F. Peterson
    •  & Nicholas J. Donato
  • Article
    | Open Access

    The secretome from cancer and stromal cells contributes to the creation of a microenvironment, which in turn contributes to invasion and angiogenesis. Here, the authors compare the secretomes of immortalized normal fibroblasts and cancer-derived fibroblast and identify CLIC3 as a driver of cancer progression.

    • Juan R. Hernandez-Fernaud
    • , Elena Ruengeler
    •  & Sara Zanivan
  • Article
    | Open Access

    Snail1 is a key factor controlling epithelial-to-mesenchymal transition and cancer metastasis. While the E3 ligases responsible for Snail1 ubiquitination and degradation have been defined, the deubiquitinating enzyme is unknown. Here Zhou and colleagues show that Dub3 stabilizes Snail1 by removing ubiquitin, thus impacting breast cancer cell metastasis.

    • Yadi Wu
    • , Yu Wang
    •  & Binhua P. Zhou
  • Article
    | Open Access

    In vitro models of actin organization show the formation of vortices, asters and stars. Here Fritzsche et al. show that such actin structures form in living cells in a manner dependent on the Arp2/3 complex but not myosin, and such structures influence membrane architecture but not cortex elasticity.

    • M. Fritzsche
    • , D. Li
    •  & C. Eggeling
  • Article
    | Open Access

    Huntington’s disease (HD) is caused by misfolding of mutant Htt protein. The authors find that in HD models, the decreased expression of heat shock transcription factor 1 that usually protects against protein misfolding, is in part caused by elevated CK2α’ kinase and Fbxw7 E3 ligase expression.

    • Rocio Gomez-Pastor
    • , Eileen T. Burchfiel
    •  & Dennis J. Thiele
  • Article
    | Open Access

    Cellular mechanical forces are regulated by Rho GTPases. Here the authors develop an optogenetic system to control the spatiotemporal activity of RhoA, and show that directing a RhoA activator to the plasma membrane causes contraction and YAP nuclear localization, whereas directing it to the mitochondria causes relaxation.

    • Léo Valon
    • , Ariadna Marín-Llauradó
    •  & Xavier Trepat
  • Article
    | Open Access

    Core clock genes, such asBmal1, are expressed in astrocytes, but their contribution to the timekeeping system is unknown. Barca-Mayo et al. report that deletion of Bmal1in Glast+ astrocytes alters the neuronal clock through GABA signalling, leading to abnormal circadian locomotor behaviour and impaired cognition in mice.

    • Olga Barca-Mayo
    • , Meritxell Pons-Espinal
    •  & Davide De Pietri Tonelli
  • Article
    | Open Access

    Angiotensin II type 1 receptor (AT1R)-mediated acute catecholamine release is modulated by β-arrestin. Here the authors show that β-arrestin-1 recruits the Ca2+channel TRPC3 and the PLCγ to the AT1R-β-arrestin complex, triggering G protein-independent calcium influx and catecholamine secretion.

    • Chun-Hua Liu
    • , Zheng Gong
    •  & Jin-Peng Sun
  • Article
    | Open Access

    Mitochondrial reactive oxygen species (ROS) promote necroptosis and the receptor interacting protein 1 (RIP1) is a key player in this form of cell death. Here, the authors show that cysteine residues in RIP1 sense ROS and oxidation of the cysteines triggers RIP1 autophosphorylation, which promotes functional necrosome formation.

    • Yingying Zhang
    • , Sheng Sean Su
    •  & Jiahuai Han
  • Article
    | Open Access

    The function of many human long non-coding RNAs (lncRNAs) is still undetermined. Here, the authors setup a gain of function CRISPR-based screen and identify a lncRNA that positively regulates AKT activity by interacting with the RNA helicase DHX9 resulting in stabilization of PI3K regulatory subunit p85.

    • Pratirodh Koirala
    • , Jianguo Huang
    •  & Yin-Yuan Mo
  • Article
    | Open Access

    The kinase FAK is important for integrin signalling and promotes cell survival. Here, the authors demonstrate FAK regulates adipocyte survival, and is particularly important for maintaining insulin sensitivity during adipose tissue expansion in the context of a calorie-rich diet.

    • Cynthia T. Luk
    • , Sally Yu Shi
    •  & Minna Woo
  • Article
    | Open Access

    The androgen receptor is crucial for the development and physiology of reproductive organs. Here the authors present the structure of the androgen receptor ligand-binding domain bound to dihydrotestosterone, identifying a homodimerization interface that is crucial for receptor activityin vivo.

    • Marta Nadal
    • , Stefan Prekovic
    •  & Eva Estébanez-Perpiñá
  • Article
    | Open Access

    Asthma is characterized by abnormal airway hyperresponsiveness. Here the authors identify BPIFA1 as a factor secreted by airway epithelial cells, and show that it regulates contractility of airway smooth muscle cells by binding to and regulating the Orai1 Ca2+channel.

    • Tongde Wu
    • , Julianne Huang
    •  & Robert Tarran
  • Article
    | Open Access

    The transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis. Here authors show that trehalose, an mTOR-independent autophagy inducer, alleviates the pathological phenotypes in a mouse model of neurodegenerative disease. Trehalose acts by inhibiting Akt, which normally suppresses TFEB via an mTORC1-independent mechanism.

    • Michela Palmieri
    • , Rituraj Pal
    •  & Marco Sardiello
  • Article
    | Open Access

    Damaged mitochondria are normally cleared through canonical and alternative autophagy pathways. Here, the authors report that mitochondria can be cleared through an autophagy-independent endosomal-lysosomal pathway that depends on Parkin-dependent sequestration of mitochondria in Rab5-positive early endosomes.

    • Babette C. Hammerling
    • , Rita H. Najor
    •  & Åsa B. Gustafsson
  • Article
    | Open Access

    The ciliary transition zone (TZ) regulates the protein and membrane composition of the primary cilium. Here the authors identify the kinesin-3 motor protein KIF13B as a regulator of TZ membrane composition that controls the ciliary accumulation of Smoothened, which is involved in activation of Sonic hedgehog signalling.

    • Kenneth B. Schou
    • , Johanne B. Mogensen
    •  & Lotte B. Pedersen
  • Article
    | Open Access

    Circadian clocks regulate physiological and behavioural rhythms. Here, the authors show that the stiffness of the extracellular environment regulates circadian clocks in murine breast epithelium via Rho signalling, and explain how extracellular matrix stiffening in aging affects circadian rhythm, with implication in disease.

    • Nan Yang
    • , Jack Williams
    •  & Qing-Jun Meng
  • Article
    | Open Access

    The transfer of ubiquitin (UB) to cellular targets is mediated sequentially by three groups of enzymes, UB activating enzyme (E1), UB conjugating enzyme (E2) and UB ligase (E3). Here the authors provide evidence that the two mammalian E1 enzymes, Uba1 and Uba6, exert biologically distinct functions.

    • Xianpeng Liu
    • , Bo Zhao
    •  & Hiroaki Kiyokawa
  • Article
    | Open Access

    Interaction of fibronectin with αv-class and α5β1 integrins results in formation of cell adhesion complexes, but the initial events (<120 s) remain unclear. Here, the authors show that αv-class integrins bind fibronectin faster than α5β1 integrins and subsequently signal to α5ß1 integrins to strengthen the adhesion.

    • Mitasha Bharadwaj
    • , Nico Strohmeyer
    •  & Daniel J. Müller
  • Article
    | Open Access

    Keratin 16 is an epithelial protein highly expressed at pressure bearing sites and during wound healing and cancer. Here the authors show that K16 interacts with the inactive protease Rhbdf2, associated with Tylosis with oesophageal cancer, and that this interaction drives increased keratinocyte proliferation.

    • Thiviyani Maruthappu
    • , Anissa Chikh
    •  & David P. Kelsell
  • Article
    | Open Access

    mTORC1 and mTORC2 are alternatively required for differentiation of T cells into Th1/Th17 or Th2 cells. Here the authors show mTORC2 signalling is also needed for IL-4-induced M2 activation with functional evidence provided by aN. brasiliensisinfection model and cold challenge to model adaptive thermogenesis.

    • R. W. Hallowell
    • , S. L. Collins
    •  & M. R. Horton
  • Article
    | Open Access

    Despite their role in oceanic CaCO3production, the physiological processes responsible for calcification in foraminifera are poorly understood Here, the authors show that calcification is driven by rapid transformation of bicarbonate to carbonate inside the cytoplasm, achieved by active outward proton pumping.

    • Takashi Toyofuku
    • , Miki Y. Matsuo
    •  & Hiroshi Kitazato
  • Article
    | Open Access

    The Snf1-related kinase (SNRK) is widely expressed and yet its function is poorly understood. Here the authors show that SNRK regulates mitochondrial coupling via the Trib3-PPARα-UCP3 pathway and that cardiac overexpression of SNRK decreases metabolic substrate usage and oxygen consumption but maintains cardiac function and energy in mice.

    • Amy K. Rines
    • , Hsiang-Chun Chang
    •  & Hossein Ardehali
  • Article
    | Open Access

    The mitotic exit network (MEN) triggers mitotic exit and can be blocked by the spindle position checkpoint (SPOC). Here the authors show that SPOC kinase Kin4 counterbalances MEN activation by the Cdc fourteen early anaphase release (FEAR) network in the mother cell and that in the absence of FEAR mitotic exit requires daughter cell-confined factors.

    • Ayse Koca Caydasi
    • , Anton Khmelinskii
    •  & Gislene Pereira
  • Article
    | Open Access

    Inhibitors of the mTORC1 pathway are considered anti-cancer drugs. Here, the authors show that on nutrient restriction, glutaminolysis-induced activation of mTORC1 induces apoptosis via inhibiting autophagy, highlighting that under such conditions inhibition of mTORC1 results in survival of cancer cells.

    • Victor H. Villar
    • , Tra Ly Nguyen
    •  & Raúl V. Durán
  • Article
    | Open Access

    Membrane fusion during exocytosis is mediated by interaction between SNARE proteins on vesicles and the cell membrane, but how SNARE complex assembly is initiated remains unknown. Here, the authors show that interaction of Sec3 with Sso2 on the plasma membrane promotes formation of an Sso2–Sec9 complex, an early step in SNARE assembly, likely by inhibiting Sso2 auto-inhibition.

    • Peng Yue
    • , Yubo Zhang
    •  & Wei Guo
  • Article
    | Open Access

    Tumour microenvironment influences the migration of cancer cells. Here the authors analyse the proteomic constitution of the extracellular matrix and identify a role for fibronectin in regulating the collective migration of squamous cell carcinoma cells.

    • Sandeep Gopal
    • , Laurence Veracini
    •  & Ellen Van Obberghen-Schilling
  • Article
    | Open Access

    Activation of YAP contributes to tumorigenesis in several tissues. Here, the authors show that in breast cancer cells glucocorticoids induce expression of fibronectin that in turn activates focal adhesion kinase/Src signalling to promote YAP nuclear translocation and transcriptional activity.

    • Giovanni Sorrentino
    • , Naomi Ruggeri
    •  & Giannino Del Sal
  • Article
    | Open Access

    Organisms improve their fitness by adjusting their gene expression to the environment, for example bacteria scale the expression of metabolic enzymes near linearly to their growth rate. Here, the authors show that such linear scaling often maximizes growth rate, but that linear scaling is suboptimal under some conditions.

    • Benjamin D. Towbin
    • , Yael Korem
    •  & Uri Alon
  • Article
    | Open Access

    Collagen has a role in cancer and is particularly important for breast cancer. Here the authors show that the expression of α3 type V collagen and one of its receptors- glipican-1- in the same cell, contributes to a deregulated growth of breast cancer cells.

    • Guorui Huang
    • , Gaoxiang Ge
    •  & Daniel S. Greenspan
  • Article
    | Open Access

    Osteoclasts are bone resorptive cells and an attractive target to treat diseases characterized by excessive bone loss, but little is known about osteoclast inhibition. Here the authors identify Gα13 as an intracellular inhibitor of osteoclastogenesis that can prevent bone loss in mice via Akt activation and inhibition of RhoA signalling.

    • Mengrui Wu
    • , Wei Chen
    •  & Yi-Ping Li