Nature Cell Biology contents: March 2012 Volume 14 Number 3, pp 223 - 329

Advertisement ZEISS on Your Campus is a free global workshop series aimed at educating scientists and students in the fundamentals of microscopy and emerging technologies in both light and electron microscopy. ZOYC 2012 will focus on the basics of acquiring images for scientific publication. The program includes lectures and hands-on sessions guided by microscopy experts. Please register: www.zeiss.com/zoyc TABLE OF CONTENTS March 2012 Volume 14, Issue 3 Editorial Review News and Views Research Highlights Articles Letters Resource Corrigendum Advertisement Celebrating 50 Years Rockland, a leader in the production of the highest quality antibodies and assays, marks 50 years of providing scientists with reagents for Cancer, Cell Biology, Cell Signaling and Neuroscience research. Manufactures near Philadelphia, PA, Rockland products are guaranteed to give predictable, repeatable results. †Protect your experiments with Rockland antibodies. Compromise elsewhere. Visit our content-rich website at www.rockland-inc.com Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement The New York Stem Cell Foundation requests applications from early career investigators in the US, Canada and the UK to cultivate innovative projects exploring fundamental areas of developmental, cellular, cognitive, and behavioral neuroscience. Proposals need not be related to stem cells. The award provides $1.5M USD over 5 years. Closing date March 30th, 2012.   Advertisement Nature.com presents Antibodypedia Finding the right antibody for the right application just got easier! Visit www.antibodypedia.com to find antibodies that have proved themselves effective for particular applications or to submit antibody validation data from your own experiments.   Editorial Top Getting to grips with Supplementary Information p223 doi:10.1038/ncb2461 Nature Cell Biology implements new guidelines for Supplementary Information. Full Text | PDF Review Top Multiple modes of cytoplasmic dynein regulation pp224 - 230 Richard B. Vallee, Richard J. McKenney and Kassandra M. Ori-McKenney doi:10.1038/ncb2420 In performing its multiple cellular functions, the cytoplasmic dynein motor is subject to complex regulation involving allosteric mechanisms within the dynein complex, as well as numerous extramolecular interactions controlling subcellular targeting and motor activity. Recent work has distinguished high- and low-load regulatory modes for cytoplasmic dynein, which, combined with a diversity of targeting mechanisms, accounts for a very broad range of functions. Full Text | PDF News and Views Top Pik1-ing clathrin adaptors pp231 - 232 Yidi Sun and David G. Drubin doi:10.1038/ncb2448 Clathrin adaptor proteins are essential for clathrin-coated vesicle biogenesis, yet the mechanisms governing their recruitment and interactions remain incompletely defined. The clathrin adaptors Gga and AP-1 are now shown to be recruited sequentially to the trans-Golgi network in two waves of clathrin coat assembly, coupled by Pik1-mediated phosphatidylinositol-4-phosphate synthesis. These findings reveal mechanistic insights into the functional and regulatory relationships between these clathrin adaptors. Full Text | PDF See also: Article by Daboussi et al. Secreted miRNAs suppress atherogenesis pp233 - 235 Daniel J. Rader and Michael S. Parmacek doi:10.1038/ncb2452 Endothelial-vascular smooth muscle cell communication has a critical role in cardiovascular homeostasis and the pathogenesis of atherosclerosis. A study now demonstrates extracellular-vesicle-mediated transfer of the atheroprotective microRNAs miR-143/145 between endothelial and vascular smooth muscle cells, providing compelling evidence that intercellular transport of miRNAs can influence a pathological process, namely atherosclerosis. Full Text | PDF See also: Article by Hergenreider et al. Good neighbours in the tumour stroma reduce oxidative stress pp235 - 236 Ralph J. DeBerardinis doi:10.1038/ncb2449 Tumour cells undergo oncogene-regulated metabolic reprogramming that maximizes survival and growth. However, little is known about metabolic interactions between tumour cells and their non-malignant neighbours in the stroma. Bone-marrow-derived stromal cells are now shown to provide cysteine, an essential nutrient that enables leukaemia cells to resist oxidative stress. Full Text | PDF See also: Article by Zhang et al. Research Highlights LncRNAs and self-renewal | Replication licensing in vivo | Genome origami | Pulling on cadherin for collective migration Cell Biology JOBS of the week Postdoctoral Research Fellow University of California San Francisco (UCSF) Postdoctoral Fellow: Developmental Glycobiology Baylor College of Medicine Research Assistant in Allergy and Immunology University of Southern California (USC) Director - Bioinformatics Core Facility University of Massachusetts Medical School Postdoctoral fellow Virginia Commonwealth University School of Medicine and the Massey Cancer Center More Science jobs from Cell Biology EVENT Cell and Developmental Biology of Xenopus 13.-24.04.12 US More science events from Articles Top Phosphoinositide-mediated clathrin adaptor progression at the trans-Golgi network pp239 - 248 Lydia Daboussi, Giancarlo Costaguta and Gregory S. Payne doi:10.1038/ncb2427 GGA proteins and the AP-1 complex are clathrin adaptors that regulate trans-Golgi network (TGN)-to-endosome traffic. Payne and colleagues show that these adaptors are recruited to the TGN in sequential waves, and reveal that phosphatidylinositol-4-monophosphate (PtdIns(4)P) coordinates the temporal assembly of these adaptors. Abstract | Full Text | PDF See also: News and Views by Sun & Drubin Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs pp249 - 256 Eduard Hergenreider, Susanne Heydt, Karine Tréguer, Thomas Boettger, Anton J. G. Horrevoets, Andreas M. Zeiher, Margot P. Scheffer, Achilleas S. Frangakis, Xiaoke Yin, Manuel Mayr, Thomas Braun, Carmen Urbich, Reinier A. Boon and Stefanie Dimmeler doi:10.1038/ncb2441 Dimmeler and colleagues show that the atheroprotective transcription factor KLF2 activates expression of the microRNAs miR-143/145 in endothelial cells. miR-143/145 are subsequently enriched in secreted microvesicles and taken up by smooth muscle cells to elicit anti-atherogenic responses. Abstract | Full Text | PDF See also: News and Views by Rader & Parmacek Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model pp257 - 265 Yifeng Xia, Narayana Yeddula, Mathias Leblanc, Eugene Ke, Yonghui Zhang, Eric Oldfield, Reuben J. Shaw and Inder M. Verma doi:10.1038/ncb2428 Verma and colleagues develop a mouse model to study the role of the NF-κB pathway in lung cancer. They show that depletion of IKK2, a kinase needed for NF-κB activation, inhibits the induction of Timp1. This suppresses the Timp-1-mediated activation of Erk, resulting in decreased tumour-cell proliferation and prolonged survival. Abstract | Full Text | PDF Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells pp266 - 275 Moussa Benhamed, Utz Herbig, Tao Ye, Anne Dejean and Oliver Bischof doi:10.1038/ncb2443 Cellular senescence is partly caused by RB1/E2F-mediated repression of proliferation genes. Bischof and colleagues now demonstrate that RB1 interacts with the microRNA effector AGO2, and that AGO2 and the microRNA let-7 are needed for chromatin remodelling and repression of E2F-target loci. Abstract | Full Text | PDF Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia pp276 - 286 Wan Zhang, Dunyaporn Trachootham, Jinyun Liu, Gang Chen, Helene Pelicano, Celia Garcia-Prieto, Weiqin Lu, Jan A. Burger, Carlo M. Croce, William Plunkett, Michael J. Keating and Peng Huang doi:10.1038/ncb2432 Chronic lymphocytic leukaemia cells depend on glutathione to counteract their high reactive oxygen species (ROS) levels. However, their ability to synthesize this antioxidant is compromised by inefficient cystine uptake. Huang and colleagues now show that bone marrow stromal cells promote leukaemia cell survival by metabolizing cystine to cysteine and releasing it into the microenvironment to be taken up by leukaemia cells. Abstract | Full Text | PDF See also: News and Views by DeBerardinis Letters Top Inferring rules of lineage commitment in haematopoiesis pp287 - 294 Cristina Pina, Cristina Fugazza, Alex J. Tipping, John Brown, Shamit Soneji, Jose Teles, Carsten Peterson and Tariq Enver doi:10.1038/ncb2442 Population-based studies in the haematopoietic system have suggested that global transcriptional noise drives lineage choice, with transcriptome-wide reversible changes occurring in self-renewing populations. Enver and colleagues use single-cell analysis to show that multipotent cells undergo independent activation of a few individual regulators that can sometimes induce a transition to the committed state. First paragraph | Full Text | PDF CLASPs prevent irreversible multipolarity by ensuring spindle-pole resistance to traction forces during chromosome alignment pp295 - 303 Elsa Logarinho, Stefano Maffini, Marin Barisic, Andrea Marques, Alberto Toso, Patrick Meraldi and Helder Maiato doi:10.1038/ncb2423 The formation of a bipolar spindle is critical for accurate segregation of the genome. Maiato and colleagues now demonstrate that CLASPs (cytoplasmic linker associated proteins) prevent spindle multipolarity in a manner independent of end-on kinetochore–microtubule attachments. They propose that CENP-E-mediated traction forces are balanced by CLASP-mediated recruitment of ninein to centriolar satellites. First paragraph | Full Text | PDF Flippase-mediated phospholipid asymmetry promotes fast Cdc42 recycling in dynamic maintenance of cell polarity pp304 - 310 Arupratan Das, Brian D. Slaughter, Jay R. Unruh, William D. Bradford, Richard Alexander, Boris Rubinstein and Rong Li doi:10.1038/ncb2444 In budding yeast, polarized Cdc42 localization is supported in part by guanine nucleotide dissociation inhibitor (GDI)-mediated extraction from the plasma membrane. Li and colleagues now show that a lipid flippase complex containing Lem3 and Dnf1 or Dnf2 contributes to membrane lipid asymmetry to facilitate GDI-mediated extraction of Cdc42. First paragraph | Full Text | PDF Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation pp311 - 317 Tomomi Kiyomitsu and Iain M. Cheeseman doi:10.1038/ncb2440 Spindle orientation depends on the tethering of microtubules to the cell cortex through LGN, NuMA and dynein/dynactin. Cheeseman and colleagues find that spindle-pole-associated Plk1 activity restricts polar dynein whereas chromosomal RanGTP negatively regulates LGN localization at the lateral cell cortex, thus identifying two differentially localized signals that modulate spindle positioning by acting on dynein-mediated forces. First paragraph | Full Text | PDF Resource Top A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response pp318 - 328 Britt Adamson, Agata Smogorzewska, Frederic D. Sigoillot, Randall W. King and Stephen J. Elledge doi:10.1038/ncb2426 Elledge and colleagues performed siRNA (short interfering RNA) screens in human cells to identify regulators of homologous recombination (HR), a mechanism for the repair of double-strand breaks in DNA. Validation of screen data reveals the susceptibility of HR siRNA screens to off-target effects but defines the heterogeneous ribonucloprotein RBMX as a regulator of HR. Abstract | Full Text | PDF Corrigendum Top The GDI-like solubilizing factor PDEδ sustains the spatial organization and signalling of Ras family proteins p329 Anchal Chandra, Hernán E. Grecco, Venkat Pisupati, David Perera, Liam Cassidy, Ferdinandos Skoulidis, Shehab A. Ismail, Christian Hedberg, Michael Hanzal-Bayer, Ashok R. Venkitaraman, Alfred Wittinghofer and Philippe I. H. Bastiaens doi:10.1038/ncb2462 Full Text | PDF Top Advertisement Announcing Principles of Biology, a textbook for the 21st century from Nature Publishing Group Principles of Biology is a peer-reviewed, affordable textbook solution for university-level Introductory Biology courses, featuring 200+ customizable learning modules, 175+ interactive exercises, 3,000+ assessment questions, and access from laptops, smartphones, or tablets. Learn more.   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

You have been sent this Table of Contents Alert because you have opted in to receive it. You can change or discontinue your e-mail alerts at any time, by modifying your preferences on your nature.com account at: www.nature.com/myaccount (You will need to log in to be recognised as a nature.com registrant) For further technical assistance, please contact our registration department For print subscription enquiries, please contact our subscription department For other enquiries, please contact our customer feedback department Nature Publishing Group | 75 Varick Street, 9th Floor | New York | NY 10013-1917 | USA Nature Publishing Group's worldwide offices: London - Paris - Munich - New Delhi - Tokyo - Melbourne San Diego - San Francisco - Washington - New York - Boston Macmillan Publishers Limited is a company incorporated in England and Wales under company number 785998 and whose registered office is located at Brunel Road, Houndmills, Basingstoke, Hampshire RG21 6XS. © 2012 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.