Nature Cell Biology contents: July 2013 Volume 15 Number 7, pp 713 - 882

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TABLE OF CONTENTS
July 2013 Volume 15, Issue 7
	Review News and Views Research Highlights Articles Letters Resources	Advertisement Roche's X-tremeGENE Transfection Reagents   Efficiently transfect difficult cells, including more than 100 cancer cell lines. Free sample and protocols at www.x-tremegene.roche.com   For life science research only. Not for use in diagnostic procedures.
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Review		Top
Emerging regulation and functions of autophagy   pp713 - 720 Patricia Boya, Fulvio Reggiori and Patrice Codogno doi:10.1038/ncb2788 Autophagy maintains cell, tissue and organism homeostasis through degradation. Codogno, Boya and Reggiori review recent data that have uncovered unexpected functions of autophagy, such as regulation of metabolism, membrane transport and modulation of host defenses.
News and Views		Top
A wake-up call for hibernating tumour cells   pp721 - 723 Sara M. Weis and David A. Cheresh doi:10.1038/ncb2794 Disseminated tumour cells (DTCs) can adopt a state of long-term dormancy. However, when and why they emerge from quiescence has remained unclear. Distinct microvascular niches are now shown to regulate this process. Mature blood vessels produce signals that sustain tumour cell quiescence, whereas sprouting microvasculature provides stimuli that reactivate DTCs, leading to metastatic relapse. See also: Article by Ghajar et al. Finding the shape-shifter genes   pp723 - 725 Michael F. Olson doi:10.1038/ncb2792 Cell morphological plasticity is controlled by intracellular signalling pathways. By combining large-scale imaging with quantitative analysis, an RNA interference (RNAi) screen in Drosophila melanogaster haemocytes reveals that most targeted genes regulate transitions between discrete shapes. Loss of gene function changes shape frequencies or reduces diversity, rather than producing new morphologies. See also: Resource by Yin et al. Sequential addition of reprogramming factors improves efficiency   pp725 - 727 X. Gaeta, Y. Xie and W. E. Lowry doi:10.1038/ncb2800 Addition of a specific set of transcription factors reprograms somatic cell nuclei to a pluripotent state. Sequential addition of these factors, rather than the simultaneous exposure used in standard protocols, improves reprogramming efficiency. This sequential method favours a transition through a state with enhanced mesenchymal characteristics before driving an epithelial transformation on the way to the pluripotent state. See also: Article by Liu et al. ULK1 targets Beclin-1 in autophagy   pp727 - 728 Volodymyr Y. Nazarko and Qing Zhong doi:10.1038/ncb2797 The substrates of mammalian ULK1/2 and its yeast homologue Atg1 in autophagy have remained elusive. The class III phosphatidylinositol 3-kinase component Beclin-1 has now been identified as a physiological substrate of the ULK kinases in autophagy following amino acid starvation, therefore suggesting a critical molecular link between the upstream kinases and the autophagy core machinery. See also: Article by Russell et al. Cell Biology JOBS of the week Senior Research Scientist in Stem Cell Biology Stanford University School of Medicine Postdoctoral Fellow In Cancer Biology and Stem Cell University of Texas Health Science Center at Houston Postdoctoral Fellow in Murine Genetics / Cancer Genomics Fred Hutchinson Cancer Research Center Chemical Biology in Cellular and Molecular Medicine University of Leuven (Belgium) Bioinformatics Postdoctoral Fellow University of California, Los Angeles (UCLA) More Science jobs from Cell Biology EVENT Cell Biology 26th September - 4th October 2013 Heidelberg, Germany More science events from
Research Highlights		Top
PTEN prevents junction instability | Collagen keeps muscle stiff for regeneration | Replication origin regulation | Macropinocytosis supports cancer cell proliferation
Articles		Top
Centrosome amplification causes microcephaly   pp731 - 740 Véronique Marthiens, Maria A. Rujano, Carole Pennetier, Sarah Tessier and Perrine Paul-Gilloteaux et al. doi:10.1038/ncb2746 Centrosome amplification is often seen in cancer cells and may cause aneuploidy. Basto and colleagues unexpectedly find that centrosome amplification (induced by Plk4 overexpression) in the mouse central nervous system causes microcephaly due to depletion of the neural stem cell pool through aneuploidy and cell death.
ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase   pp741 - 750 Ryan C. Russell, Ye Tian, Haixin Yuan, Hyun Woo Park and Yu-Yun Chang et al. doi:10.1038/ncb2757 The protein kinase ULK1 regulates autophagy induction but its mode of action is poorly understood. Guan and colleagues show that following nutrient starvation, ULK1-mediated phosphorylation of Beclin-1 is required for the activation of VPS34 lipid kinase within the autophagy complex ATG1–VPS34–Beclin-1. They also find that during starvation, the inhibitory effect of mTOR on ULK1 is relieved to increase the phosphorylation of Beclin-1. See also: News and Views by Nazarko & Zhong
Matrix geometry determines optimal cancer cell migration strategy and modulates response to interventions   pp751 - 762 Melda Tozluoğlu, Alexander L. Tournier, Robert P. Jenkins, Steven Hooper and Paul A. Bates et al. doi:10.1038/ncb2775 Sahai and colleagues present a computational model of cell motility based on experimentally derived parameters. They show that the model predicts the behaviour of cells in in vitro and in vivo settings with respect to the migration strategy and response of cancer cells to specific experimental interventions.
Chase-and-run between adjacent cell populations promotes directional collective migration   pp763 - 772 Eric Theveneau, Benjamin Steventon, Elena Scarpa, Simon Garcia and Xavier Trepat et al. doi:10.1038/ncb2772 Mayor and colleagues observed that placodal cell movements in Xenopus and zebrafish embryos are controlled by their interaction with adjacent neural crest cells. Neural crest cells chemotactically migrated towards placodal cells and, on contact, induced neural crest cells to migrate away, revealing a ‘chase-and-run’ behaviour.
A Bcl-xL–Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis   pp773 - 785 Hongmei Li, Kambiz N. Alavian, Emma Lazrove, Nabil Mehta and Adrienne Jones et al. doi:10.1038/ncb2791 Recovery of neurotransmitter involves the endocytic retrieval of vesicles from the plasma membrane. Jonas and colleagues show that in hippocampal synapses, the anti-apoptotic protein Bcl-xL enhances the recovery of a vesicle pool. It does this independently of its mitochondrial function, through its calmodulin-stimulated translocation to clathrin-coated pits and recruitment of the dynamin-related protein Drp1.
Microtubules and Alp7–Alp14 (TACC–TOG) reposition chromosomes before meiotic segregation   pp786 - 796 Yasutaka Kakui, Masamitsu Sato, Naoyuki Okada, Takashi Toda and Masayuki Yamamoto doi:10.1038/ncb2782 Chromosome segregation requires the capture of kinetochores by microtubules, a process that in yeast mitosis is facilitated by kinetochores being tethered to spindle poles. Sato and colleagues find that in meiosis I, when kinetochores are not tethered to poles, a microtubule array associated with TACC (Alp7) and TOG proteins (Alp14 and Dis1) retrieves kinetochores in a Polo-kinase-dependent manner.
Emi1 preferentially inhibits ubiquitin chain elongation by the anaphase-promoting complex   pp797 - 806 Weiping Wang and Marc W. Kirschner doi:10.1038/ncb2755 The Emi1 protein inhibits the anaphase promoting complex (APC), an E3 ubiquitin ligase and critical cell cycle regulator, but it has remained unclear how it does this. Wang and Kirschner demonstrate that Emi1 suppresses the elongation of ubiquitin chains on APC substrates by interfering in different ways with the activities of the E2 enzymes UBCH10 and Ube2S.
The perivascular niche regulates breast tumour dormancy   pp807 - 817 Cyrus M. Ghajar, Héctor Peinado, Hidetoshi Mori, Irina R. Matei and Kimberley J. Evason et al. doi:10.1038/ncb2767 Bissell, Ghajar and colleagues use organotypic culture systems and in vivo mouse and zebrafish models to reveal the distinct effects of different microvascular niches on tumour cell dormancy. They report that although the stable microvasculature promotes cancer cell quiescence through the production of thrombospondin-1, cancer cells residing near neovascular tips are induced to grow through the action of TGF-β and periostin. See also: News and Views by Weis & Cheresh
TRF2 inhibits a cell-extrinsic pathway through which natural killer cells eliminate cancer cells   pp818 - 828 Annamaria Biroccio, Julien Cherfils-Vicini, Adeline Augereau, Sébastien Pinte and Serge Bauwens et al. doi:10.1038/ncb2774 Gilson and colleagues report that increased expression of the telomeric protein TRF2 in tumour cells promotes tumorigenesis in a non-cell-autonomous manner, by inhibiting the recruitment and activation of natural killer cells at the tumour site.
Sequential introduction of reprogramming factors reveals a time-sensitive requirement for individual factors and a sequential EMT–MET mechanism for optimal reprogramming   pp829 - 838 Xiaopeng Liu, Hao Sun, Jing Qi, Linli Wang and Songwei He et al. doi:10.1038/ncb2765 Pei and colleagues show that introduction of the pluripotency reprogramming factors in sequence (Oct4–Klf4, c-Myc and finally Sox-2), rather than introducing them all together, increases reprogramming efficiency. This sequential delivery activates the epithelial-to-mesenchymal transition (EMT) before the mesenchymal-to-epithelial transition (MET), which was previously reported to occur during reprogramming. The authors also show that addition of EMT modulators influences reprogramming in a similar manner. See also: News and Views by Gaeta et al.
Letters		Top
A spindle-independent cleavage pathway controls germ cell formation in Drosophila    pp839 - 845 Ryan M. Cinalli and Ruth Lehmann doi:10.1038/ncb2761 Emergence of primordial germ cells (PGCs) from the syncytial Drosophila embryo is not well understood. Lehmann and colleagues show that a cytokinetic furrow emerges for PGC formation that does not require a canonical anaphase spindle cleavage pathway but involves regulators of the small GTPase Rho and the BTB-domain protein Germ cell-less.
BMI1 represses Ink4a/Arf and Hox genes to regulate stem cells in the rodent incisor   pp846 - 852 Brian Biehs, Jimmy Kuang-Hsien Hu, Nicolas B. Strauli, Eugenio Sangiorgi and Heekyung Jung et al. doi:10.1038/ncb2766 The polycomb protein BMI1 has been linked to maintenance of adult stem cells. Klein and colleagues find that BMI1 is also required for the maintenance of stem cells in the continuously growing mouse incisor, through repression of the Ink4a/Arf locus to modulate the proliferation of stem cells and repression of Hox genes to prevent inappropriate lineage decisions in stem cell progeny.
In vitro contraction of cytokinetic ring depends on myosin II but not on actin dynamics   pp853 - 859 Mithilesh Mishra, Jun Kashiwazaki, Tomoko Takagi, Ramanujam Srinivasan and Yinyi Huang et al. doi:10.1038/ncb2781 Mabuchi, Balasubramanian and colleagues develop a system to study the contraction of the fission yeast contractile ring in vitro. They identify components required for this process and find that myosin ATPase activity, but not actin disassembly, is needed.
Resources		Top
A screen for morphological complexity identifies regulators of switch-like transitions between discrete cell shapes   pp860 - 871 Zheng Yin, Amine Sadok, Heba Sailem, Afshan McCarthy and Xiaofeng Xia et al. doi:10.1038/ncb2764 Bakal, Wong and colleagues performed an RNAi screen in Drosophila cells, as well as imaging and systems-level analyses, to identify genes regulating morphological complexity in heterogeneous cell populations. They report that rather than generating novel shapes, most genes control a switch-like transition between distinct morphologies. The authors also extend their findings to mouse and human melanoma cells. See also: News and Views by Olson
Proteomic and genomic approaches reveal critical functions of H3K9 methylation and heterochromatin protein-1γ in reprogramming to pluripotency   pp872 - 882 Rupa Sridharan, Michelle Gonzales-Cope, Constantinos Chronis, Giancarlo Bonora and Robin McKee et al. doi:10.1038/ncb2768 Plath and colleagues survey the global histone modification changes linked to reprogramming. They delineate that the H3K9-methylation-associated protein Cbx3 restricts late events of reprogramming and, in particular, prevents the expression of the pluripotent gene Nanog.
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