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Table of Contents

01 October 2011; volume 12, issue 10

Upfront

Editorial

  • These are your rights
    1. Howy Jacobs

    Science is a vocation, not a job, and requires a degree of dedication and sacrifice that does not apply in a standard workplace. Howy proposes that we should be more upfront about this brutal reality when advising prospective scientists about their career choices.

    Howy Jacobs
    Published online 01.10.2011

Opinion

  • Unended knights' tournaments
    1. Ladislav Kováč1
    1. 1 Comenius University, Bratislava, Slovakia

    Richard Dawkins introduced a generation of biologists to the influential idea of ‘selfish genes’. But the implicit genocentrism of his hypothesis is increasingly challenged.

    Ladislav Kováč
    Published online 01.10.2011

Hot off the Press

  • The structural diversity in α1‐antitrypsin misfolding
    1. Stephen P Bottomley1
    1. 1 Department of Biochemistry and Molecular Biology, Monash University, Victoria, 3800, Australia

    The structure of α1‐antitrypsin polymers, which cause a devastating disease, is vigorously debated. Here, the state of the field is discussed in view of a paradigm‐changing structure published in this issue of EMBO reports.

    Stephen P Bottomley
    Published online 01.10.2011
  • Metabolic signals regulate SIRT1 expression
    1. Angeliki Chalkiadaki1 and
    2. Leonard Guarente1
    1. 1 Paul F. Glenn Lab and Department of Biology, MIT, Cambridge, Massachusetts, USA

    SIRT1 is a key metabolic regulator in response to nutrient availability. Here, Chalkiadaki and Guarente comment on a report published online this month in which J. Auwerx and colleagues show how SIRT1 transcription is controlled by the antagonistic actions of CREB and ChREBP in response to the energetic status of the cell.

    Angeliki Chalkiadaki, Leonard Guarente
    Published online 23.09.2011

Meeting Point

  • Lineage commitments: emphasis on embryonic–extraembryonic interfaces
    1. Karen M Downs1
    1. 1 University of Wisconsin‐Madison, Madison, Wisconsin, USA

    The EMBO Workshop on ‘Lineage Commitments: Emphasis on Embryonic–Extraembryonic Interfaces’, held in May 2011, demonstrated that embryonic and extraembryonic tissues play early and significant interacting roles that mutually promote each other's further and correct deployment within the mammalian conceptus.

    Karen M Downs
    Published online 01.10.2011

Correspondence

  • Of mice and men
    1. Thomas C Erren1,
    2. J Valérie Groß2,
    3. Melissa S Koch2 and
    4. V Benno Meyer‐Rochow3,4
    1. 1 Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research at the University of Cologne, Germany
    2. 2 Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research
    3. 3 School of Engineering and Science, Jacobs University Bremen, Germany
    4. 4 Departments of Biology and Physiology of the University of Oulu, Finland

    Thomas Erren and colleagues point out that studies on light and circadian rhythmicity in humans have their own interesting pitfalls, of which all researchers should be mindful.

    Thomas C Erren, J Valérie Groß, Melissa S Koch, V Benno Meyer‐Rochow
    Published online 01.10.2011

Science & Society

Outlook

Feature

Review

  • The interplay between morphogens and tissue growth
    1. Andrés Dekanty1 and
    2. Marco Milán*,1,2
    1. 1 Institute for Research in Biomedicine (IRB Barcelona), 10–12, 08028, Barcelona, Spain
    2. 2 Institució Catalana de Recerca i Estudis Avançats (ICREA) Baldiri Reixac, 10–12, 08028, Barcelona, Spain
    1. ↵*Corresponding author. Tel: +34 93 403 4902; Fax: +34 93 403 7109 E-mail: marco.milan{at}irbbarcelona.org

    Morphogens are long known diffusible molecules that regulate organ patterning and size in animals. The authors discuss in this review recent findings concerning the reciprocal interactions between tissue growth and morphogen signalling and how these interactions may help specify cellular fates, organ size and even organ shape.

    • morphogens
    • growth
    • limb development
    • Drosophila
    • vertebrate
    • Received June 3, 2011.
    • Accepted August 10, 2011.
    Andrés Dekanty, Marco Milán
    Published online 01.10.2011

Scientific Reports

  • Molecular basis of α1‐antitrypsin deficiency revealed by the structure of a domain‐swapped trimer
    1. Masayuki Yamasaki1,†‡,
    2. Timothy J Sendall1,
    3. Mary C Pearce2,
    4. James C Whisstock2,3 and
    5. James A Huntington*,1
    1. 1 Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK
    2. 2 Department of Biochemistry, and ARC Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria, 3800, Australia
    3. 3 ARC Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria, 3800, Australia
    1. ↵*Corresponding author. Tel: +44 1223 763 230; Fax: +44 1223 336 827; E-mail: jah52{at}cam.ac.uk

    1. ↵† These authors contributed equally to this work

    • ↵‡ Present address: Department of Molecular and Cellular Biology, Kyoto University, Institute for Frontier Medical Sciences, Sakyo‐ku, Kyoto 606‐8397, Japan

    The structure of the toxic oligomeric species of α1‐antitrypsin is unexpectedly different from what had been proposed and enabled by the domain swap of the carboxy‐terminal 34 residues. Such oligomers react with an antibody that recognizes aggregates in patients and are shown to occur in vivo.

    • serpin
    • crystal structure
    • polymer
    • domain swap
    • Received June 27, 2011.
    • Revision received July 20, 2011.
    • Accepted July 22, 2011.
    Masayuki Yamasaki, Timothy J Sendall, Mary C Pearce, James C Whisstock, James A Huntington
    Published online 01.10.2011
  • The transcription factor Krox20 is an E3 ligase that sumoylates its Nab coregulators
    1. Pablo García‐Gutiérrez1,
    2. Francisco Juárez‐Vicente1,
    3. Francisco Gallardo‐Chamizo1,
    4. Patrick Charnay2 and
    5. Mario García‐Domínguez*,1
    1. 1 Stem Cells, CABIMER (CSIC), Avenida Americo Vespucio, Seville, E‐41092, Spain
    2. 2 IBENS, Inserm U1024, CNRS UMR 8197, Paris, 75230, France
    1. ↵*Corresponding author. Tel: +34 954 468201; Fax: +34 954 461664; E-mail: mario.garcia{at}cabimer.es

    Krox20—a key regulator of hindbrain development—is shown to have SUMO E3 ligase activity towards Nab proteins, which are Krox20 coregulators. Nab SUMOylation enhances the repression of endogenous targets by the Krox20:Nab complex.

    • Krox20
    • Nab
    • SUMO ligase
    • Ubc9
    • Received February 7, 2011.
    • Revision received July 1, 2011.
    • Accepted July 1, 2011.
    Pablo García‐Gutiérrez, Francisco Juárez‐Vicente, Francisco Gallardo‐Chamizo, Patrick Charnay, Mario García‐Domínguez
    Published online 01.10.2011
  • The mRNA export factor Npl3 mediates the nuclear export of large ribosomal subunits
    1. Alexandra Hackmann1,
    2. Thomas Gross1,†,
    3. Claudia Baierlein1 and
    4. Heike Krebber*,1
    1. 1 Abteilung für Molekulare Genetik, Institut für Mikrobiologie und Genetik, Göttinger Zentrum für Molekulare Biowissenschaften, Georg‐August Universität Göttingen, Grisebachstrasse 8, Göttingen, 37077, Germany
    1. ↵*Corresponding author. Tel: +49 551 39 3801; Fax: +49 551 39 3805; E-mail: heike.krebber{at}biologie.uni-goettingen.de

    • ↵† Present address: Department of Genetics, Harvard Medical School, 77 avenue Louis Pasteur, Boston, Massachusetts 02115, USA

    This study reports the discovery of a new function of the mRNA export factor Npl3 in mediating pre‐60S ribosomal subunit export. Npl3 interacts with the 25S rRNA, ribosomal and ribosome‐associated proteins, and with the nuclear pore complex.

    • mRNA export
    • ribosome transport
    • pre‐60S export
    • export receptor
    • RNA‐binding protein
    • Received December 9, 2010.
    • Revision received June 21, 2011.
    • Accepted June 28, 2011.
    Alexandra Hackmann, Thomas Gross, Claudia Baierlein, Heike Krebber
    Published online 01.10.2011
  • Lac operator repeats generate a traceable fragile site in mammalian cells
    1. Ariana Jacome1 and
    2. Oscar Fernandez‐Capetillo*,1
    1. 1 Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid, 28029, Spain
    1. ↵*Corresponding author. Tel: +34 91 732 8000 ext. 3480; Fax: +34 91 732 8028; E-mail: ofernandez{at}cnio.es

    Endogenous fragile sites in chromosomes can only be detected after their breakage. In this report, the authors find that insertion of lac operator repeats generate fragile sites that can be followed throughout the cell cycle and show that oncogenes promote the formation of anaphase bridges and micronuclei containing fragile sites.

    • anaphase bridge
    • PICH
    • common fragile site
    • lac operon
    • micronucleus
    • Received March 15, 2011.
    • Revision received June 21, 2011.
    • Accepted July 8, 2011.
    Ariana Jacome, Oscar Fernandez‐Capetillo
    Published online 01.10.2011
  • Open Access
    Drosophila syndecan regulates tracheal cell migration by stabilizing Robo levels
    1. Joachim G Schulz1,2,3,
    2. Helga Ceulemans1,3,
    3. Emmanuel Caussinus4,
    4. Maria F Baietti1,3,
    5. Markus Affolter4,
    6. Bassem A Hassan*,2,3 and
    7. Guido David*,1,3
    1. 1 Laboratory of Glycobiology and Developmental Genetics, Katholieke Universiteit Leuven, Herestraat 49 bus 602, KU Leuven, Leuven, 3000, Belgium
    2. 2 Laboratory of Neurogenetics, Flanders Institute for Biotechnology (VIB), Katholieke Universiteit Leuven, Herestraat 49 bus 602, KU Leuven, Leuven, 3000, Belgium
    3. 3 Department of Human Genetics, Center for Human Genetics, Katholieke Universiteit Leuven, Herestraat 49 bus 602, KU Leuven, Leuven, 3000, Belgium
    4. 4 Growth and Development, Biozentrum der Universität Basel, Basel, 4056, Switzerland
    1. ↵*Corresponding authors. Tel: +32 16 346218; Fax: +32 16 346226; E-mail: bassem.hassan{at}cme.vib-kuleuven.be or Tel: +32 16 345863; Fax: +32 16 347166; E-mail: guido.david{at}cme.vib-kuleuven.be

    Syndecans have crucial roles in cell adhesion, polarization and migration through their interaction with a range of extracellular ligands. The authors show in this report that Drosophila syndecan is required for the extension and fusion of the dorsal branches of the tracheal system, by reducing Slit/Robo signalling levels.

    • cell migration
    • Drosophila
    • heparan sulphate
    • Robo
    • tracheal system
    • Received November 9, 2010.
    • Revision received June 14, 2011.
    • Accepted June 27, 2011.

    This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

    Joachim G Schulz, Helga Ceulemans, Emmanuel Caussinus, Maria F Baietti, Markus Affolter, Bassem A Hassan, Guido David
    Published online 01.10.2011
  • Yan, an ETS‐domain transcription factor, negatively modulates the Wingless pathway in the Drosophila eye
    1. Emily R Olson1,
    2. Raluca Pancratov1,
    3. Sujash S Chatterjee1,
    4. Binita Changkakoty1,
    5. Zeeshan Pervaiz1 and
    6. Ramanuj DasGupta*,1
    1. 1 Cancer Institute and Department of Pharmacology, New York University School of Medicine, 522 First Avenue, Smilow Research Building, Room 1211, New York, New York, 10016, USA
    1. ↵*Corresponding author. Tel: +1 212 263 9247; Fax: +1 212 263 9210; E-mail: ramanuj.dasgupta{at}nyumc.org

    1. These authors contributed equally to this work

    Yan is a conserved ETS transcriptional repressor that regulates EGF receptor signalling in Drosophila. In this report, the authors show that in addition to its known function in the EGF receptor pathway, Yan also negatively regulates the Wingless pathway in the Drosophila eye, and that this regulation is required for proper retinal development.

    • crosstalk
    • RNAi
    • Wingless
    • Wnt
    • Yan
    • Received January 13, 2011.
    • Revision received July 7, 2011.
    • Accepted July 8, 2011.
    Emily R Olson, Raluca Pancratov, Sujash S Chatterjee, Binita Changkakoty, Zeeshan Pervaiz, Ramanuj DasGupta
    Published online 01.10.2011
  • LGR4 and LGR5 are R‐spondin receptors mediating Wnt/β‐catenin and Wnt/PCP signalling
    1. Andrei Glinka1,
    2. Christine Dolde1,
    3. Nadine Kirsch1,
    4. Ya‐Lin Huang1,
    5. Olga Kazanskaya1,
    6. Dierk Ingelfinger2,
    7. Michael Boutros2,
    8. Cristina‐Maria Cruciat*,1 and
    9. Christof Niehrs*,1,3
    1. 1 Division of Molecular Embryology, DKFZ‐‐ZMBH Alliance, DKFZ, Im Neuenheimer Feld 580, Heidelberg, D‐69120, Germany
    2. 2 Division of Signalling and Functional Genomics, DKFZ and University of Heidelberg, Im Neuenheimer Feld 580, Heidelberg, D‐69120, Germany
    3. 3 Institute of Molecular Biology, Mainz, 55128, Germany
    1. ↵*Corresponding authors. Tel: +49 6221 42 4391; Fax: +49 6221 42 4692; E-mail: c.cruciat{at}dkfz-heidelberg.de or Tel: +49 6221 42 4690; Fax: +49 6221 42 4692; E-mail: niehrs{at}dkfz-heidelberg.de

    1. These authors contributed equally to this work

    R‐spondins are secreted proteins known to synergize with Wnt signalling. The authors now show that R‐spondins are ligands for LGR4 and LGR5 orphan G‐protein‐coupled receptors. Binding of R‐spondins to LGRs positively regulates both Wnt/ ‐catenin and Wnt/PCP signalling pathways in vivo.

    • endocytosis
    • LGR4
    • LGR5
    • R‐spondin
    • Wnt
    • Received July 14, 2011.
    • Revision received August 8, 2011.
    • Accepted August 10, 2011.
    Andrei Glinka, Christine Dolde, Nadine Kirsch, Ya‐Lin Huang, Olga Kazanskaya, Dierk Ingelfinger, Michael Boutros, Cristina‐Maria Cruciat, Christof Niehrs
    Published online 01.10.2011
  • Open Access
    Sir2 histone deacetylase prevents programmed cell death caused by sustained activation of the Hog1 stress‐activated protein kinase
    1. Alexandre Vendrell1,
    2. Mar Martínez‐Pastor2,
    3. Alberto González‐Novo1,
    4. Amparo Pascual‐Ahuir2,
    5. David A Sinclair3,
    6. Markus Proft2 and
    7. Francesc Posas*,1
    1. 1 Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, E‐08003, Valencia, Spain
    2. 2 Department of Biotechnology, Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia‐CSIC, Ingeniero Fausto Elio s/n, E‐46011, Valencia, Spain
    3. 3 Department of Pathology and Glenn Labs for Aging Research, Harvard Medical School, Boston, Massachusetts, 02115, USA
    1. ↵*Corresponding author. Tel: +34 93 316 0849; Fax: +34 93 316 0901; E-mail: francesc.posas{at}upf.edu

    1. These authors contributed equally to this work

    Sustained activation of Hog1 in yeast inhibits mitochondrial respiration and leads to ROS accumulation, which causes cell death. Activation of Sir2 in response to Hog1 activation relieves the Hog1‐ induced oxidative stress and prevents cell death.

    • cell death
    • Hog1
    • SCF
    • SAPK
    • Sir2
    • Received May 22, 2011.
    • Revision received June 26, 2011.
    • Accepted June 29, 2011.

    This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.

    Alexandre Vendrell, Mar Martínez‐Pastor, Alberto González‐Novo, Amparo Pascual‐Ahuir, David A Sinclair, Markus Proft, Francesc Posas
    Published online 01.10.2011
  • CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability
    1. Lilia G Noriega1,†,
    2. Jérôme N Feige1,‡,
    3. Carles Canto1,
    4. Hiroyasu Yamamoto1,
    5. Jiujiu Yu1,
    6. Mark A Herman2,
    7. Chikage Mataki1,
    8. Barbara B Kahn2 and
    9. Johan Auwerx*,1
    1. 1 Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratory of Integrative and Systems Physiology and Nestlé Chair in Energy Metabolism, 1015, Lausanne, Switzerland
    2. 2 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, 02215, USA
    1. ↵*Corresponding author. Tel: +41 21 693 95 22; Fax: +41 21 693 9600; E-mail: admin.auwerx{at}epfl.ch

    • ↵† Present address: Instituto Nacional de Ciencias Médicas y Nutrición ‘Salvador Zubirán, 14000 México DF, México

    • ↵‡ Present address: Novartis Institute for Biomedical Research, 4056 Basel, Switzerland

    The deacetylase SIRT1 is a metabolic regulator that is activated in situations of energy stress. The authors connect energy‐sensing to transcriptional programmes, demonstrating that SIRT1 expression is controlled by the positive effect of CREB under energy stress, and the negative effect of ChREBP under normal conditions.

    • SIRT1
    • CREB
    • ChREBP
    • glucagon
    • nutrient availability
    • Received January 22, 2011.
    • Revision received June 16, 2011.
    • Accepted June 17, 2011.
    Lilia G Noriega, Jérôme N Feige, Carles Canto, Hiroyasu Yamamoto, Jiujiu Yu, Mark A Herman, Chikage Mataki, Barbara B Kahn, Johan Auwerx
    Published online 01.10.2011
  • Open Access
    Independent localization of MAP2, CaMKIIα and β‐actin RNAs in low copy numbers
    1. Martin Mikl1,
    2. Georgia Vendra*,1,† and
    3. Michael A Kiebler*,1
    1. 1 Center for Brain Research, Department of Neuronal Cell Biology, Medical University of Vienna, Spitalgasse 4, Wien, 1090, Austria
    1. ↵*Corresponding authors. Tel: 00 43 1 40160 34254; Fax: 00 43 1 40160 934253; E-mail: georgia.vendra{at}meduniwien.ac.at or Tel: 00 43 1 40160 34250; Fax: 00 43 1 40160 934253; E-mail: michael.kiebler{at}meduniwien.ac.at

    1. ↵† These authors contributed equally to this work

    mRNA subcellular localization in neurons involves the formation of ribonucleoprotein particles (RNPs) that are transported through the cytoskeleton. The authors show that, unexpectedly, dendritic RNPs contain few molecules of mRNA and both the nature of these mRNAs and their number are tightly controlled.

    • RNA localization
    • β‐actin
    • CaMKIIα
    • MAP2 mRNA
    • Staufen 2
    • Received February 3, 2011.
    • Revision received June 8, 2011.
    • Accepted June 22, 2011.

    This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.

    Martin Mikl, Georgia Vendra, Michael A Kiebler
    Published online 01.10.2011
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In this Issue
Volume 12, Number 10
01 October 2011
EMBO reports: 12 (10)
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