Nature Cell Biology contents: July 2012 Volume 14 Number 7, pp 651 - 774

Advertisement Roche's X-tremeGENE Transfection Reagents Transfect efficiently with low cytotoxicity - proven in 250 different cell types...over 100 cancer cells. Free sample and protocols at www.x-tremegene.roche.com For life science research only. Not for use in diagnostic procedures TABLE OF CONTENTS July 2012 Volume 14, Issue 7 Comment News and Views Research Highlights Articles Letters Resources Advertisement BD Pharmingen™ transcription factor buffer set This newly optimized fixation and permeabilization buffer system improves sensitivity for many transcription factors including FoxP3, RORyt, T-bet, Bcl-6, and others. Request a free sample and get connected to high-sensitivity detection of intracellular and intranuclear proteins with flow cytometry. bdbiosciences.com/go/tfbuffer Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Solution savings: Best-in-class bead-based immunoassays With a combined value package you can save 10% on the BD Accuri™ C6 personal flow cytometer, 40% on BD™ CBA reagents for 2 full years, plus $6,500 worth of free software and cytometer options. There's never been a better time to buy the best-in-class solution for bead-based immunoassays. bdbiosciences.com/go/CBA   Advertisement Online-only personal subscriptions now available to Nature Cell Biology and Nature Structural Molecular Biology For only 49 USD/29 GBP/29 EUR Subscribe now!   Comment Top Evolutionary cell biology: Lessons from diversity   p651 Frances M. Brodsky, Mukund Thattai and Satyajit Mayor doi:10.1038/ncb2539 Novel perspectives emerge from a recent conference on the origins of eukaryotic cells, which covered phylogenetics, population genetics and evolutionary consequences of energy requirements and host-pathogen interactions. News and Views Top Defining an epidermal stem cell epigenetic network   pp652 - 653 Salvador Aznar Benitah doi:10.1038/ncb2538 Dynamic changes in the chromatin of adult stem cells are required to establish the gene expression profiles associated with stem cell self-renewal and differentiation. A complex genetic network of chromatin remodellers and epigenetic factors orchestrate these genome-wide changes in human epidermal stem cells. See also: Resource by Mulder et al. Get on the exosome bus with ALIX   pp654 - 655 James H. Hurley and Greg Odorizzi doi:10.1038/ncb2530 Exosomes have a growing inventory of functions, but the mechanism of protein sorting into exosomes has been unclear. Now, a signal sequence first described in viral budding provides just such a cargo sorting mechanism, revealing closer-than-expected parallelism between exosome biogenesis and the ESCRT-dependent endolysosomal pathway. See also: Article by Baietti et al. Ubiquitin removal in the TGF-β pathway   pp656 - 657 Kamna Aggarwal and Joan Massagué doi:10.1038/ncb2534 The transforming growth factor (TGF-β) pathway is regulated by ubiquitin-mediated proteolysis at different levels. Two studies now identify deubiquitinating enzymes (DUBs) for the TGF-β type I receptor. Both ubiquitin-specific peptidase-4 (USP4) and -15 (USP15) extend the life of activated receptors against the negative pressure of receptor-ubiquitinating complexes, but through distinct modes of action. See also: Article by Zhang et al. Research Highlights Cyclin keeps dNTPs in balance | Glycine fuels cancer cells | Visualizing tumour propagation and metastasis in vivo | miRNAs and cell-cycle control in ESCs Cell Biology JOBS of the week Postdoctoral Fellowship (two years) � Development of Novel Peripheral Blood Stem Cell Collection And Separation Technology University of Lund Contribution to the development of metal-supported high temperature fuel cells MINES ParisTech Postdoctoral Position: Gene Regulation in Breast Cancer / Stem Cell Biology UC --- College of Medicine Scientific Editor, Cell Metabolism Elsevier Inc. Research Associate, Stem Cell Biology / Neuroscience University of Cardiff More Science jobs from Cell Biology EVENT 10th International Congress on Cell Biology 25.-28.07.12 Brazil More science events from Articles Top The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r    pp659 - 665 Andrew Keniry, David Oxley, Paul Monnier, Michael Kyba, Luisa Dandolo, Guillaume Smits and Wolf Reik doi:10.1038/ncb2521 Reik and colleagues show that deletion of the large intergenic non-coding RNA H19 leads to unlimited placenta growth. They find that the H19 RNA contains a microRNA that targets the insulin-like growth factor receptor IGF-1R, and demonstrate that the RNA-binding protein HuR prevents miR-675 excision from H19 until miR-675 activity is required to halt placenta growth. Caenorhabditis elegans screen reveals role of PAR-5 in RAB-11-recycling endosome positioning and apicobasal cell polarity   pp666 - 676 Julia Franziska Winter, Sebastian Höpfner, Kerstin Korn, Benjamin O. Farnung, Charles R. Bradshaw, Giovanni Marsico, Michael Volkmer, Bianca Habermann and Marino Zerial doi:10.1038/ncb2508 RAB-11-positive recycling endosomes participate in the establishment and maintenance of epithelial polarity. Zerial and colleagues carry out an in vivo image-based RNAi screen for factors that regulate recycling endosome positioning in Caenorhabditis elegans. They identify, among other candidates, PAR-5 as a key determinant of recycling endosome positioning and, thus, apicobasal polarity. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes   pp677 - 685 Maria Francesca Baietti, Zhe Zhang, Eva Mortier, Aurélie Melchior, Gisèle Degeest, Annelies Geeraerts, Ylva Ivarsson, Fabienne Depoortere, Christien Coomans, Elke Vermeiren, Pascale Zimmermann and Guido David doi:10.1038/ncb2502 Exosomes are increasingly recognized as key intermediaries of intercellular communication, yet the mechanisms governing their biogenesis remain unclear. Zimmermann, David and colleagues report that interactions between the transmembrane protein syndecan, its associated protein syntenin and the ESCRT adaptor ALIX are necessary for exosome formation, supporting a role for the ESCRT machinery in this process. See also: News and Views by Hurley & Odorizzi PRR5L degradation promotes mTORC2-mediated PKC-δ phosphorylation and cell migration downstream of Gα12    pp686 - 696 Xiaoqing Gan, Jiyong Wang, Chen Wang, Eeva Sommer, Tohru Kozasa, Srinivasa Srinivasula, Dario Alessi, Stefan Offermanns, Melvin I. Simon and Dianqing Wu doi:10.1038/ncb2507 Wu and colleagues delineate an mTORC2-dependent cell migration pathway. They show that stimulation of the Gα12 protein subunit induces the ARAF/ERK-mediated expression of the RFFL E3 ubiquitin ligase. RFFL, in turn, targets the inhibitory PRR5L subunit of the mTORC2 complex for ubiquitylation and degradation, enabling mTORC2 to phosphorylate PKC-δ and promote cell migration. miR-129-3p controls cilia assembly by regulating CP110 and actin dynamics   pp697 - 706 Jingli Cao, Yidong Shen, Lei Zhu, Yanan Xu, Yizhuo Zhou, Zhili Wu, Yiping Li, Xiumin Yan and Xueliang Zhu doi:10.1038/ncb2512 Ciliogenesis requires the removal of CP110 from the mother centriole, and is influenced by actin dynamics. Zhu and colleagues now show that the microRNA miR-129-3p controls primary cilia formation in vertebrates by downregulating CP110 and targeting multiple actin regulators to suppress actin dynamics. ER network formation requires a balance of the dynamin-like GTPase Sey1p and the Lunapark family member Lnp1p   pp707 - 716 Shuliang Chen, Peter Novick and Susan Ferro-Novick doi:10.1038/ncb2523 The endoplasmic reticulum (ER) forms an intricate network of interconnected tubules. Sey1 is known to govern tubule formation, but the proteins that counteract tubule fusion remained unclear. Chen, Novick and Ferro-Novick propose that Lnp1 antagonizes the activity of Sey1 to modulate ER network formation. USP4 is regulated by AKT phosphorylation and directly deubiquitylates TGF-β type I receptor   pp717 - 726 Long Zhang, FangFang Zhou, Yvette Drabsch, Rui Gao, B. Ewa Snaar-Jagalska, Craig Mickanin, Huizhe Huang, Kelly-Ann Sheppard, Jeff A. Porter, Chris X. Lu and Peter ten Dijke doi:10.1038/ncb2522 Ten Dijke and colleagues identify USP4 as a deubiquitylating enzyme (DUB) for the TGF-β receptor I in a screen for ubiquitin-specific proteases affecting TGF-β signalling. USP4, present in a complex with other DUBs, is regulated by AKT-mediated phosphorylation and is required for TGF-β-induced breast cancer cell migration and metastasis. See also: News and Views by Aggarwal & Massagué c-Abl promotes osteoblast expansion by differentially regulating canonical and non-canonical BMP pathways and p16INK4a expression   pp727 - 737 Hui-Yi Kua, Huijuan Liu, Wai Fook Leong, Lili Li, Deyong Jia, Gang Ma, Yuanyu Hu, Xueying Wang, Jenny F. L. Chau, Ye-Guang Chen, Yuji Mishina, Sharon Boast, James Yeh, Li Xia, Guo-Qiang Chen, Lin He, Stephen P. Goff and Baojie Li doi:10.1038/ncb2528 Li and colleagues report that c-Abl regulates the responses downstream of bone morphogenetic protein (BMP) that direct proliferation or senescence in osteoblasts. They show that phosphorylation of the BMP receptor BMPR1A by c-Abl promotes downstream Smad-mediated responses and osteoblast expansion, whereas in the absence of c-Abl, BMP activates Erk signalling, leading to p16INK4a-induced senescence. Letters Top The S. pombe cytokinesis NDR kinase Sid2 activates Fin1 NIMA kinase to control mitotic commitment through Pom1/Wee1   pp738 - 745 Agnes Grallert, Yvonne Connolly, Duncan L. Smith, Viesturs Simanis and Iain M. Hagan doi:10.1038/ncb2514 In fission yeast, the septum initiation network (SIN) regulates septation at the end of mitosis. Hagan and colleagues now reveal a further role for the SIN kinase Sid2 that is independent of other known SIN components, in the control of entry into mitosis through phosphorylation of the NIMA kinase Fin1. MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC components   pp746 - 752 Yuya Yamagishi, Ching-Hui Yang, Yuji Tanno and Yoshinori Watanabe doi:10.1038/ncb2515 The kinase MPS1 is a conserved and essential component of the spindle assembly checkpoint (SAC), but its relevant substrate in this context has remained uncertain. Watanabe and colleagues now show that, in fission yeast and human cells, MPS1 (Mph1 in fission yeast) phosphorylates the kinetochore protein KNL1 (Spc7), leading to kinetochore recruitment of BUB1, an event required for SAC activation. Resources Top Diverse epigenetic strategies interact to control epidermal differentiation   pp753 - 763 Klaas W. Mulder, Xin Wang, Carles Escriu, Yoko Ito, Roland F. Schwarz, Jesse Gillis, Gábor Sirokmány, Giacomo Donati, Santiago Uribe-Lewis, Paul Pavlidis, Adele Murrell, Florian Markowetz and Fiona M. Watt doi:10.1038/ncb2520 Watt and colleagues carried out an RNAi screen to identify epigenetic modifiers involved in the control of epidermal differentiation. They delineate a network of genetic interactions using a Bayesian mixture model approach, and uncover two complexes of modifiers that differentially affect self-renewal and differentiation of epidermal stem cells. See also: News and Views by Benitah Genome-wide RNAi screening identifies human proteins with a regulatory function in the early secretory pathway   pp764 - 774 Jeremy C. Simpson, Brigitte Joggerst, Vibor Laketa, Fatima Verissimo, Cihan Cetin, Holger Erfle, Mariana G. Bexiga, Vasanth R. Singan, Jean-Karim Hériché, Beate Neumann, Alvaro Mateos, Jonathon Blake, Stephanie Bechtel, Vladimir Benes, Stefan Wiemann, Jan Ellenberg and Rainer Pepperkok doi:10.1038/ncb2510 Pepperkok, Simpson and colleagues performed genome-wide RNAi screens in human cells to uncover regulators of the secretory pathway. They also identify protein networks with previously unappreciated roles in secretory pathway regulation. Top Advertisement Nature Cell Biology FOCUS ON CILIOGENESIS Cilia are dynamic organelles that modulate various developmental and physiological processes. Perturbation of cilia function has been linked to a range of diseases. Nature Cell Biology presents a collection of Research articles published in the journal in the past few years that highlights current knowledge of cilia biogenesis and function. Access the Focus online: www.nature.com/ncb/webfocus/ciliogenesis   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

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