Nature Cell Biology contents: January 2013 Volume 15 Number 1, pp 1 - 124

TABLE OF CONTENTS January 2013 Volume 15, Issue 1 Editorial Review News and Views Research Highlights Articles Letters Resources Corrigenda Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Outlook: Ageing Research into the mechanisms of ageing is yielding insights, many of them diet-related, into how we might not only live longer but stay healthier as we do. Access the Outlook free online for six months. Produced with support from: Nestlé Research Center   Editorial Top Focusing on the cell biology of cancer   p1 doi:10.1038/ncb2667 This month, we launch a series of specially commissioned review and perspective articles on cancer cell biology, covering key topics and recent advances in understanding the cellular mechanisms underlying cancer. Review Top p53 mutations in cancer   pp2 - 8 Patricia A. J. Muller and Karen H. Vousden doi:10.1038/ncb2641 News and Views Top 'Goldilocks' suppressor screen identifies web of polarity regulators   pp9 - 10 Geraldine Seydoux doi:10.1038/ncb2666 Genome sequencing and RNAi have been powerful allies in the quest to assign function to every gene. Systematic RNAi screens identify essential genes efficiently, but are less effective with pleiotropic or redundant genes. A common trick used by geneticists to overcome this problem is to screen for genetic interactors — mutations that enhance or suppress the phenotype of a starting mutation. Now, this classic approach has been combined with the versatility of RNAi to generate an expanded gene network for cell polarity. See also: Resource by Fievet et al. Anthrax receptors position the spindle   pp11 - 13 Nicolas Minc and Matthieu Piel doi:10.1038/ncb2664 Spindle orientation plays a pivotal role in tissue morphogenesis. An asymmetric anthrax receptor cap is revealed to promote activation of a formin to orient the spindle along the planar cell polarity (PCP) axis in zebrafish dorsal epiblast cells. See also: Article by Castanon et al. Humans put their eggs in more than one basket   pp13 - 15 Diana J. Laird doi:10.1038/ncb2665 Primordial germ cell (PGC) development in the human fetus remains relatively uncharted. A new study suggests that epigenetic reprogramming and sex differentiation in human PGCs occur asynchronously over an extended time period. This finding raises questions and implications for in vitro PGC differentiation. See also: Resource by Gkountela et al. Cell Biology JOBS of the week Postdoctoral Associates in Cell and Cancer Biology Vanderbilt University Postdoctoral Fellow and Research Associate Positions in Stem Cell Biology Children's Hospital Oakland Research Institute (CHORI) PhD Position in Cell Biology at the Max Planck Institute of Molecular Physiology: Function and Regulation of Microtubule Networks Max Planck Institute of Molecular Physiology Postdoctoral Positions in Stem Cell Biology and Epigenetics University of Wisconsin School of Medicine and Public Health Laboratory Heads: Developmental Biology and Stem Cell Biology RIKEN Center for Developmental Biology (CDB) More Science jobs from Cell Biology EVENT CELLTech 2013 22nd Jan - 23rd Jan 2013 CA, US More science events from Research Highlights Top Mad1 doubles as nuclear import regulator | The haematopoiesis transcription landscape | SAICAR drives cancer cell survival | Inducing necrosis with SIRTainty Articles Top An integrin–ILK–microtubule network orients cell polarity and lumen formation in glandular epithelium   pp17 - 27 Nasreen Akhtar and Charles H. Streuli doi:10.1038/ncb2646 Mammary gland morphogenesis involves the polarization of epithelial cells and the formation of a lumen. Akhtar and Streuli demonstrate that β1 integrin and the downstream kinase ILK at the basement membrane are required for polarization in this system, through orientation of microtubules and Golgi positioning. Anthrax toxin receptor 2a controls mitotic spindle positioning   pp28 - 39 I. Castanon, L. Abrami, L. Holtzer, C. P. Heisenberg, F. G. van der Goot and M. González-Gaitán doi:10.1038/ncb2632 The Wnt/planar cell polarity (Wnt/PCP) pathway orients cell division in various developmental contexts including zebrafish gastrulation. Gonzalez-Gaitan and colleagues reveal that, downstream of Wnt/PCP, the anthrax toxin receptor 2a interacts with actin to form a cortical actin cap in dorsal epiblast cells, and acts through RhoA and the formin zDia2 to orient the mitotic spindle. See also: News and Views by Minc & Piel Phosphorylation-enabled binding of SGO1–PP2A to cohesin protects sororin and centromeric cohesion during mitosis   pp40 - 49 Hong Liu, Susannah Rankin and Hongtao Yu doi:10.1038/ncb2637 Accurate chromosome segregation requires that sister-chromatid cohesion is resolved first at chromosome arms in prophase and then at centromeres in metaphase. In prophase, centromeric cohesion is protected by shugoshin and protein phosphase 2A (SGO1–PP2A). Yu and colleagues show that CDK1-mediated phosphorylation of SGO1 promotes SGO1–PP2A binding to cohesin, and dephosphorylation of the cohesion-promoting component sororin to prevent cohesin removal. A human genome-wide screen for regulators of clathrin-coated vesicle formation reveals an unexpected role for the V-ATPase   pp50 - 60 Patrycja Kozik, Nicola A. Hodson, Daniela A. Sahlender, Nikol Simecek, Christina Soromani, Jiahua Wu, Lucy M. Collinson and Margaret S. Robinson doi:10.1038/ncb2652 Robinson and colleagues perform a human-genome-wide siRNA screen to identify regulators of clathrin-coated vesicle formation. The knockdown phenotype of one of their hits, V-ATPase, is rescued by exogenous cholesterol, revealing an intriguing link between cholesterol and clathrin-coated vesicle formation. Salt-inducible kinases regulate growth through the Hippo signalling pathway in Drosophila    pp61 - 71 Michael C. Wehr, Maxine V. Holder, Ieva Gailite, Rebecca E. Saunders, Tobias M. Maile, Elena Ciirdaeva, Rachael Instrell, Ming Jiang, Michael Howell, Moritz J. Rossner and Nicolas Tapon doi:10.1038/ncb2658 An intriguing intersection between the AMPK and Hippo signalling pathways provides fresh insight into how nutrient availability regulates cell growth. Tapon and colleagues show that Drosophila salt-inducible kinases (Sik2/3), members of the AMPK family, phosphorylate the Hippo pathway protein Sav to attenuate Hippo signalling and promote Yki transcriptional activity. SCFFbxo9 and CK2 direct the cellular response to growth factor withdrawal via Tel2/Tti1 degradation and promote survival in multiple myeloma   pp72 - 81 Vanesa Fernández-Sáiz, Bianca-Sabrina Targosz, Simone Lemeer, Ruth Eichner, Christian Langer, Lars Bullinger, Clemens Reiter, Julia Slotta-Huspenina, Sonja Schroeder, Anna-Maria Knorn, Julia Kurutz, Christian Peschel, Michele Pagano, Bernhard Kuster and Florian Bassermann doi:10.1038/ncb2651 The mTORC1 complex promotes protein translation and cell growth, whereas mTORC2 promotes survival. The Tel2 and Tt1 proteins belong to both complexes. Bassermann and colleagues demonstrate that following growth-factor deprivation, casein kinase 2 mediates phosphorylation of Tel2 and Tt1, specifically in the mTORC2 complex, to target them for degradation by the SCFFbxo9 ubiquitin ligase. This mechanism inactivates mTORC1 and activates mTORC2 and Akt signalling to promote survival of multiple myeloma cells. Letters Top Pivoting of microtubules around the spindle pole accelerates kinetochore capture   pp82 - 87 Iana Kalinina, Amitabha Nandi, Petrina Delivani, Mariola R. Chacón, Anna H. Klemm, Damien Ramunno-Johnson, Alexander Krull, Benjamin Lindner, Nenad Pavin and Iva M. Tolic-Nørrelykke doi:10.1038/ncb2640 To segregate chromosomes, spindle microtubules must attach to chromosomes through kinetochores, in a process involving several types of microtubule behaviour. Tolic-Norrelykke and colleagues find that fission yeast microtubules rapidly rotate around the spindle poles, and mathematical modelling confirms that this random microtubule movement facilitates kinetochore capture. Centrosomal MPF triggers the mitotic and morphogenetic switches of fission yeast   pp88 - 95 Agnes Grallert, Avinash Patel, Victor A. Tallada, Kuan Yoow Chan, Steven Bagley, Andrea Krapp, Viesturs Simanis and Iain M. Hagan doi:10.1038/ncb2633 The Cdc2 (also called Cdk1) kinase is first activated at the centrosome to initiate mitosis in human cells. Hagan and colleagues demonstrate that in fission yeast, Cdc2 and Polo kinase activation at the spindle pole body remotely controls not only mitotic commitment but also ‘new end take off’, the initiation of bipolar growth in G2. Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan   pp96 - 102 Darren J. Baker, Meelad M. Dawlaty, Tobias Wijshake, Karthik B. Jeganathan, Liviu Malureanu, Janine H. van Ree, Ruben Crespo-Diaz, Santiago Reyes, Lauren Seaburg, Virginia Shapiro, Atta Behfar, Andre Terzic, Bart van de Sluis and Jan M. van Deursen doi:10.1038/ncb2643 The amount of the BubR1 checkpoint protein declines with age in mouse models, suggesting that it has a role in ageing. Van Deursen and colleagues reveal that expressing a BubR1 transgene in mice reduces tumorigenesis and aneuploidy, and delays ageing-related phenotypes. Resources Top Systematic genetic interaction screens uncover cell polarity regulators and functional redundancy   pp103 - 112 Bruno Thomas Fievet, Josana Rodriguez, Sundar Naganathan, Christine Lee, Eva Zeiser, Takao Ishidate, Masaki Shirayama, Stephan Grill and Julie Ahringer doi:10.1038/ncb2639 Cell polarity is important for the function of many animal cells, and several aspects of its establishment are conserved across species, from worm to human. Ahringer and colleagues have performed large-scale genetic interaction screens in Caenorhabditis elegans to identify a network of polarity regulators that includes genes not previously associated with polarity, such as the nuclear pore protein NPP-2. See also: News and Views by Seydoux The ontogeny of cKIT + human primordial germ cells proves to be a resource for human germ line reprogramming, imprint erasure and in vitro differentiation   pp113 - 122 Sofia Gkountela, Ziwei Li, John J. Vincent, Kelvin X. Zhang, Angela Chen, Matteo Pellegrini and Amander T. Clark doi:10.1038/ncb2638 Clark and colleagues have characterized the stages during which global epigenetic reprogramming occurs in human primordial germ cells, and delineate the appearance of these changes at 16 days of differentiation. See also: News and Views by Laird Corrigenda Top MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism   p123 Karthik Mallilankaraman, César Cárdenas, Patrick J. Doonan, Harish C. Chandramoorthy, Krishna M. Irrinki, Tünde Golenár, György Csordás, Priyanka Madireddi, Jun Yang, Marioly Müller, Russell Miller, Jill E. Kolesar, Jordi Molgó, Brett Kaufman, György Hajnóczky, J. Kevin Foskett and Muniswamy Madesh doi:10.1038/ncb2669 PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK- and IRE1α-mediated unfolded protein response   p123 Miri Jwa and Paul Chang doi:10.1038/ncb2670 EGFR signalling as a negative regulator of Notch1 gene transcription and function in proliferating keratinocytes and cancer   p124 Vihren Kolev, Anna Mandinova, Juan Guinea-Viniegra, Bing Hu, Karine Lefort, Chiara Lambertini, Victor Neel, Reinhard Dummer, Erwin F. Wagner and G. Paolo Dotto doi:10.1038/ncb2676 ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect   p124 Weiwei Yang, Yanhua Zheng, Yan Xia, Haitao Ji, Xiaomin Chen, Fang Guo, Costas A. Lyssiotis, Kenneth Aldape, Lewis C. Cantley and Zhimin Lu doi:10.1038/ncb2677 Top Advertisement Do you want to save money on your lab costs? 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