Cell growth

  • Article
    | Open Access

    Hypertrophic cardiomyocytes switch their metabolism from fatty acid oxidation to glucose use, but the functional role of this change is unclear. Here the authors show that high intracellular glucose inhibits the degradation of branched-chain amino acids, which is required for the activation of pro-growth mTOR signaling.

    • Dan Shao
    • , Outi Villet
    •  & Rong Tian
  • Article
    | Open Access

    The actin-like protein MreB coordinates the synthesis of the cell wall, which determines cell shape in bacteria. Here, Bratton et al. show that the transmembrane protein RodZ modulates MreB polymer number and curvature preference, contributing to the cylindrical uniform shape of E. coli cells.

    • Benjamin P. Bratton
    • , Joshua W. Shaevitz
    •  & Randy M. Morgenstein
  • Article
    | Open Access

    MicroRNAs play important roles in endothelial cells injury, proliferation and maladaptation by negatively regulating posttranscriptional gene expression. Here the authors uncover the role of the long non coding RNA lncWDR59, target of miR-103, in endothelial maladaptation.

    • Lucia Natarelli
    • , Claudia Geißler
    •  & Andreas Schober
  • Article
    | Open Access

    Single CD34 negative haematopoietic stem cells (HSCs) can fully reconstitute lympho-myeloid hematopoiesis in mice. Here, using single cell transplantation and gene expression analyses, the authors show that CD34 negative HSCs lie at the apex of haematopoiesis in human cord blood and that they can give rise to erythroid megakaryocytic progenitors.

    • Keisuke Sumide
    • , Yoshikazu Matsuoka
    •  & Yoshiaki Sonoda
  • Article
    | Open Access

    The Hippo pathway is a major orchestrator of organ development and homeostasis. Here Azad and colleagues develop a biosensor to monitor the activity of the Hippo pathway component LATS and identify VEGF signalling as an upstream regulator of LATS, supporting a role for Hippo signalling during angiogenesis.

    • T. Azad
    • , H. J. Janse van Rensburg
    •  & X. Yang
  • Article
    | Open Access

    The Ras/Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways are essential for cancer cell survival. Here, the authors describes a molecule a131 with dual-inhibitory properties, which targets PI5P4K and mitosis, and it is involved in Ras/Raf/MEK/ERK and PI3K/Akt/mTOR crosstalk, thereby causing reversible growth arrest in normal cells and cell death of tumor cells.

    • Mayumi Kitagawa
    • , Pei-Ju Liao
    •  & Sang Hyun Lee
  • Article
    | Open Access

    The mechanisms regulating cardiomyocyte proliferation during development and cardiac regeneration are incompletely understood. The authors show that the transcription factor REST regulates cardiomyocyte proliferation by binding and repressing the cell cycle inhibitor p21.

    • Donghong Zhang
    • , Yidong Wang
    •  & Bin Zhou
  • Article
    | Open Access

    Target of rapamycin (TOR) kinase operates within two distinct multiprotein complexes named TORC1 and TORC2. Here the authors report a cryo-EM structure of TORC2, establish its subunit organization, providing a rationale for TORC2’s rapamycin insensitivity and the mutually exclusive inclusion of Avo3/Rictor or Raptor within their respective TOR complex.

    • Manikandan Karuppasamy
    • , Beata Kusmider
    •  & Christiane Schaffitzel
  • Article
    | Open Access

    Tip-growing cells can find their growing path toward the source of attractive signals. Here, using experimental data and mathematical modeling, Luo et al. demonstrate that tip-localized exocytosis can integrate guidance cues with Rho GTPase signaling to control cell wall mechanics and direct tip growth in Arabidopsis pollen tubes.

    • Nan Luo
    • , An Yan
    •  & Zhenbiao Yang
  • Article
    | Open Access

    Polo-like kinase 1 (Plk1) is a key regulator of mitosis. Here, the authors show that Plk1 activates the pentose phosphate pathway in cancer cells by directly phosphorylating glucose-6-phosphate dehydrogenase (G6PD) and that such activation is critical for cell cycle progression and cancer cell growth.

    • Xiaoyu Ma
    • , Lin Wang
    •  & Huafeng Zhang
  • Article
    | Open Access

    Plants lack the amino acid sensors that regulate TOR in metazoans. Here Dong et al. show that Arabidopsis GCN2 senses carbon and nitrogen availability for cysteine synthesis while sulfur limitation activates TOR via glucose metabolism, providing a mechanism whereby plants control growth according to nutrient availability.

    • Yihan Dong
    • , Marleen Silbermann
    •  & Markus Wirtz
  • Article
    | Open Access

    The quiescence-exit process is noisy even in genetically identical cells under the same environmental conditions. Here the authors show that the heterogeneity of quiescence exit reflects a memory of preceding cell growth at quiescence induction and immediate division history prior to quiescence entry.

    • Xia Wang
    • , Kotaro Fujimaki
    •  & Guang Yao
  • Article
    | Open Access

    Protein MreB participates in elongation of sidewalls during growth of most rod-shaped bacteria. Here, the authors use fluorescence microscopy and single-particle tracking to visualize MreB, showing thatBacillus subtilis and Escherichia coliappear to use different strategies to adapt to growth rate variations.

    • Cyrille Billaudeau
    • , Arnaud Chastanet
    •  & Rut Carballido-López
  • Article
    | Open Access

    In response to gut epithelial damage,Drosophilastem cells proliferate to produce large polyploid enterocytes (EC), which comprise the bulk of the epithelium. Here, the authors show that stress-dependent EGFR/MAP kinase signalling drives both endoreplication and cell growth in newborn ECs.

    • Jinyi Xiang
    • , Jennifer Bandura
    •  & Bruce A. Edgar
  • Article
    | Open Access

    The mechanistic coupling of cell growth and cell cycle control with cell size regulation in tissues is not well understood. Here, the authors show that within the shoot apical meristem of Arabidopsis cell size depends on developmental stage, genotype and environmental signals; however cell growth and cell division are cell-autonomously coordinated.

    • Angharad R. Jones
    • , Manuel Forero-Vargas
    •  & James A. H. Murray
  • Article
    | Open Access

    Stat4 is a transcription factor known to regulate pro-inflammatory signalling. Here, Menget al. show that Stat4 is not only regulating inflammation but it is also crucial for great vessels development and endothelial precursor proliferation in zebrafish, by inhibiting the expression of hdac3and counteracting the effect of Stat1a.

    • Zhao-Zheng Meng
    • , Wei Liu
    •  & Yong Zhou
  • 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

    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

    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

    Inhibition of PI3K/mTOR, which mimics nutrient starvation, causes death of detached but not matrix-attached cancer cells. Here the authors show that nutrient restriction of epithelial cells causes uptake of the matrix protein laminin, which results in increased intracellular amino acids and enhanced mTORC1 signalling.

    • Taru Muranen
    • , Marcin P. Iwanicki
    •  & Nada Y. Kalaany
  • Article
    | Open Access

    Oncogenic mutations of isocitrate dehydrogenases 1 and 2 result in the production of the oncometabolite R-2-hydroxyglutarate. Here the authors show that the oncometabolite promotes mTOR activation in a PTEN/PI3K-independent manner by regulating DEPTOR stability via inhibition of KDM4A activity.

    • Mélissa Carbonneau
    • , Laurence M. Gagné
    •  & Frédérick A. Mallette
  • Article
    | Open Access

    How genetic diversity generates complex phenotypes along a continuum remains a fundamental question of biology. Here—applying the emerging SWATH proteomics technology—the authors describe a proteome wide association study (PWAS) of Drosophila wing size and identify functional protein clusters associated with this trait.

    • Hirokazu Okada
    • , H. Alexander Ebhardt
    •  & Ernst Hafen
  • Article
    | Open Access

    Mrf4 is a transcription factor important for muscle development, but despite high expression its function in adults is unknown. Here the authors show that interfering with Mrf4 in adult mice leads to muscle hypertrophy by activating MEF2-dependent transcription and promoting protein synthesis.

    • Irene Moretti
    • , Stefano Ciciliot
    •  & Stefano Schiaffino
  • Article
    | Open Access

    Branching morphogenesis is essential for the formation of most epithelial organs. Here, the authors show that Neurofibromatosis 2 (NF2), the Hippo pathway kinases LATS1 and LATS2, and the transcriptional co-activators YAP and TAZ control tip identity, RET signalling and branching morphogenesis in the mouse kidney.

    • Antoine Reginensi
    • , Leonie Enderle
    •  & Helen McNeill
  • Article
    | Open Access

    The molecular mechanisms regulating myelination are only partially understood. Here authors show that Tsc1ablation in oligodendrocyte lineage activates ER stress and apoptotic programs in mice, and that enhancing PERK-eIF2α signalling partially rescues the myelination defects in Tsc1 mutants.

    • Minqing Jiang
    • , Lei Liu
    •  & Q. Richard Lu
  • Article
    | Open Access

    Ceruloplasmin has an important role in the stabilization and nuclear transport of HIF-1α, thus regulating VEGF expression. Here the authors show that the transcription factor SARI reduces colorectal cancer growth and angiogenesis in vivoby inducing the degradation of ceruloplasmin, thereby inhibiting the HIFα/VEGF axis.

    • Lei Dai
    • , Xueliang Cui
    •  & Hongxin Deng
  • Article
    | Open Access

    14-3-3 proteins regulate several signalling pathways but often act redundantly; however, the molecular mechanisms behind such redundancy are unclear. Here, the authors show that 14-3-3 proteins regulate two interacting components of Tor signalling in Drosophila, Tctp and Rheb, disrupting organ development.

    • Thao Phuong Le
    • , Linh Thuong Vuong
    •  & Kwang-Wook Choi
  • Article
    | Open Access

    Circular RNAs are formed from exon back-splicing, the significance of these endogenous RNAs is beginning to be unraveled. Here, the authors identify thousands of circular RNAs differentially expressed between normal and cancer tissues and show that an abundant circular RNA generated from HIPK3regulates cell growth.

    • Qiupeng Zheng
    • , Chunyang Bao
    •  & Shenglin Huang
  • Article
    | Open Access

    mTORC1 is crucial for chondrocyte proliferation and bone growth, but the downstream signalling is not clear. Here, the authors use rapamycin and chondrocyte-specific Tsc1 knockout mice to show that S6K1 can cause nuclear accumulation of Gli2, thus driving PTHrP expression and preventing terminal differentiation of prehypertrophic chondrocytes.

    • Bo Yan
    • , Zhongmin Zhang
    •  & Xiaochun Bai
  • Article
    | Open Access

    Ternary complex (TC) and eIF4F complex assembly are rate-limiting steps in translation initiation that are regulated by eIF2α phosphorylation and the mTOR/4E-BP pathway. Here the authors show that the protein kinases mTORC1 and CK2 coordinate TC and eIF4F complex assembly through eIF2β to stimulate cell proliferation.

    • Valentina Gandin
    • , Laia Masvidal
    •  & Ivan Topisirovic
  • Article
    | Open Access

    Drosophila neural stem cells (NSCs) are quiescent at early larval stages but how this is regulated is unclear. Here, Ding et al. show that quiescence of NSCs is mediated by cell-contact inhibition via the Hippo pathway transmembrane proteins Crumbs and Echinoid, which in turn are regulated by nutrient levels.

    • Rouven Ding
    • , Kevin Weynans
    •  & Christian Berger
  • Article
    | Open Access

    The Set8-Set7 methyltransferase plays a critical role in cell cycle progression and tumorigenesis, and is degraded through modification by the E3 ubiquitin ligase CRL4Cdt2. Here Wang et al. identify SCFβ-TRCPas an additional E3 ubiquitin ligase that marks Set8 for degradation in response to DNA damage.

    • Zhiwei Wang
    • , Xiangpeng Dai
    •  & Wenyi Wei
  • Article
    | Open Access

    Research on the gut microbiota would benefit from improved methods to study microbial population growth. Here, Myhrvold et al. present a ‘mark and recapture’ method that uses genetically encoded fluorescent particles to measure the growth rates of gut microbes in live animals.

    • Cameron Myhrvold
    • , Jonathan W. Kotula
    •  & Pamela A. Silver
  • Article
    | Open Access

    AMPK senses cellular energy and switches off pathways involved in protein and fatty acid synthesis, but the selectivity of AMPK for different pathways is unclear. Here, the authors show that PIAS4-dependent SUMOylation and inactivation of AMPK preferentially restores activity of the mTORC1 pathway.

    • Yan Yan
    • , Saara Ollila
    •  & Tomi P. Mäkelä
  • Article
    | Open Access

    SETDB1 is a histone methyltransferase and a role for the protein has been proposed in cancer. Here, the authors show that SETDB1 contributes to hepatocellular cancer by preferably forming a complex with mutant p53, resulting in di-methylation of a critical lysine residue and stabilization of the protein.

    • Qi Fei
    • , Ke Shang
    •  & Jianyong Shou
  • Article
    | Open Access

    In fission yeast, cell growth is co-ordinated with division by the cell tip-localized DYRK kinase Pom1, which inhibits the medially placed mitotic activator Cdr2. Here, Kelkar and Martin show that, upon glucose starvation, microtubules are destabilized in a PKA-dependent manner, leading to the deposition of Pom1 at cell sides where it delays mitosis.

    • Manasi Kelkar
    •  & Sophie G. Martin