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Table of Contents

01 July 2018; volume 19, issue 7

Opinion

  • Biology, a science of greys
    Biology, a science of greys
    1. Jordi Casanova (jcrbmc{at}ibmb.csic.es)1
    1. 1Institut de Biologia Molecular de Barcelona (CSIC)/Institute for Research in Biomedicine Barcelona, The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

    Models and categories are useful research tools in biology but they do not necessarily represent reality. To better understand life's complexity and avoid pointless controversies, we need to be more aware of their limitations.

    EMBO Reports (2018) 19: e46332

    Jordi Casanova
    Published online 01.06.2018

Science & Society

Scientific Reports

  • Open Access
    The β3‐integrin endothelial adhesome regulates microtubule‐dependent cell migration
    The β3‐integrin endothelial adhesome regulates microtubule‐dependent cell migration
    1. Samuel J Atkinson1,
    2. Aleksander M Gontarczyk1,
    3. Abdullah AA Alghamdi1,
    4. Tim S Ellison1,
    5. Robert T Johnson1,
    6. Wesley J Fowler1,
    7. Benjamin M Kirkup1,
    8. Bernardo C Silva1,
    9. Bronwen E Harry1,
    10. Jochen G Schneider2,3,
    11. Katherine N Weilbaecher4,
    12. Mette M Mogensen1,
    13. Mark D Bass5,
    14. Maddy Parsons6,
    15. Dylan R Edwards7 and
    16. Stephen D Robinson (stephen.robinson{at}uea.ac.uk)*,1
    1. 1School of Biological Sciences, Norwich Research Park, University of East Anglia, Norwich, UK
    2. 2Luxembourg Center for Systems Biomedicine (LCSB), Luxembourg & Saarland University Medical Center, Internal Medicine II, University of Luxembourg, Homburg, Germany
    3. 3Centre Hospitalier Emily Mayrisch, Esch, Luxembourg
    4. 4Division of Molecular Oncology, Department of Internal Medicine, Washington University in St Louis, St. Louis, MO, USA
    5. 5Department of Biomedical Science, Centre for Membrane Interactions and Dynamics, University of Sheffield, Sheffield, UK
    6. 6Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guys Campus, London, UK
    7. 7Faculty of Medicine and Health Sciences, Norwich Research Park, University of East Anglia, Norwich, UK
    1. ↵*Corresponding author. Tel: +44 1603 591756; E‐mail: stephen.robinson{at}uea.ac.uk

    Engagement of αvβ3‐integrin with fibronectin at mature focal adhesions localises an Rcc2/Anxa2/Rac1 containing complex to these sites, preventing Rac1 from stabilising microtubules. When αvβ3 is not present, the complex associates with α5β1‐integrin instead, resulting in increased microtubule stability.

    Synopsis

    Engagement of αvβ3‐integrin with fibronectin at mature focal adhesions localises an Rcc2/Anxa2/Rac1 containing complex to these sites, preventing Rac1 from stabilising microtubules. When αvβ3 is not present, the complex associates with α5β1‐integrin instead, resulting in increased microtubule stability.

    • β3‐integrin regulates localisation of tubulin subunits to the endothelial adhesome.

    • Angiogenic processes both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3‐integrin levels are reduced.

    • Active Rac1 cellular associations change with depletion of β3‐integrin.

    • adhesome
    • endothelial
    • integrins
    • microtubules

    EMBO Reports (2018) 19: e44578

    • Received June 5, 2017.
    • Revision received April 25, 2018.
    • Accepted April 27, 2018.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Samuel J Atkinson, Aleksander M Gontarczyk, Abdullah AA Alghamdi, Tim S Ellison, Robert T Johnson, Wesley J Fowler, Benjamin M Kirkup, Bernardo C Silva, Bronwen E Harry, Jochen G Schneider, Katherine N Weilbaecher, Mette M Mogensen, Mark D Bass, Maddy Parsons, Dylan R Edwards, Stephen D Robinson
    Published online 24.05.2018
  • Structural insights into Rhino‐Deadlock complex for germline piRNA cluster specification
    Structural insights into Rhino‐Deadlock complex for germline piRNA cluster specification
    1. Bowen Yu1,†,
    2. Yu An Lin2,†,
    3. Swapnil S Parhad3,
    4. Zhaohui Jin1,
    5. Jinbiao Ma4,
    6. William E Theurkauf3,
    7. ZZ Zhao Zhang (zzhang{at}carnegiescience.edu)*,2 and
    8. Ying Huang (huangy{at}sibcb.ac.cn)*,1
    1. 1State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Shanghai Science Research Center, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
    2. 2Department of Embryology, Carnegie Institution for Science, Baltimore, MD, USA
    3. 3Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
    4. 4State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Department of Biochemistry, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai, China
    1. ↵* Corresponding author. Tel: +1 4102463092; E‐mail: zzhang{at}carnegiescience.edu
      Corresponding author. Tel: +86 2120778200; E‐mail: huangy{at}sibcb.ac.cn

    1. ↵† These authors contributed equally to this work

    Rhino recruits Deadlock through a novel interacting mode that is crucial to piRNA biogenesis and transposon silencing. Key amino acid differences determine the cross‐species incompatibility between Drosophila melanogaster and Drosophila simulans.

    Synopsis

    Rhino recruits Deadlock through a novel interacting mode that is crucial to piRNA biogenesis and transposon silencing. Key amino acid differences determine the cross‐species incompatibility between Drosophila melanogaster and Drosophila simulans.

    • The crystal structures of Rhino‐Deadlock complex from melanogaster and simulans indicate that one Rhino CSD domain binds the HhH motif of one Deadlock through a novel interface.

    • Disrupting the interface leads to infertility and transposon hyperactivation in flies, indicating the crucial role of Rhino‐Deadlock machinery in piRNA biogenesis.

    • The structures highlight that the cross‐species incompatibility is due to electrostatic repulsion caused by amino acid differences between the two species.

    • chromoshadow domain
    • cross‐species incompatibility
    • Deadlock
    • HP1
    • piRNA cluster
    • Rhino

    EMBO Reports (2018) 19: e45418

    • Received November 2, 2017.
    • Revision received April 28, 2018.
    • Accepted May 14, 2018.
    Bowen Yu, Yu An Lin, Swapnil S Parhad, Zhaohui Jin, Jinbiao Ma, William E Theurkauf, ZZ Zhao Zhang, Ying Huang
    Published online 01.06.2018
  • DnaQ exonuclease‐like domain of Cas2 promotes spacer integration in a type I‐E CRISPR‐Cas system
    DnaQ exonuclease‐like domain of Cas2 promotes spacer integration in a type I‐E CRISPR‐Cas system
    1. Gediminas Drabavicius1,
    2. Tomas Sinkunas1,
    3. Arunas Silanskas1,
    4. Giedrius Gasiunas1,2,
    5. Česlovas Venclovas1 and
    6. Virginijus Siksnys (siksnys{at}ibt.lt)*,1
    1. 1Institute of Biotechnology, Vilnius University, Vilnius, Lithuania
    2. 2Present Address: CasZyme, Vilnius, Lithuania
    1. ↵*Corresponding author. Tel: +370 5 2234354; E‐mail: siksnys{at}ibt.lt

    The CRISPR4‐Cas system of the Streptococcus thermophilus spacer integration complex contains the Cas2‐DnaQ fusion protein. This study shows that the DnaQ domain is required for the processing of the protospacers prior to integration into the CRISPR array.

    Synopsis

    The CRISPR4‐Cas system of the Streptococcus thermophilus spacer integration complex contains the Cas2‐DnaQ fusion protein. This study shows that the DnaQ domain is required for the processing of the protospacers prior to integration into the CRISPR array.

    • The DnaQ domain fused to Cas2 in the S. thermophilus CRISPR4‐Cas system is a 3′–5′ exonuclease.

    • The DnaQ domain in the Cas1:Cas2‐DnaQ complex trims 3′ ends of protospacers to generate overhangs optimal for integration.

    • Cas1:Cas2‐DnaQ integrates trimmed protospacers into the CRISPR array.

    • adaptation
    • Cas1
    • Cas2
    • protospacer
    • Streptococcus thermophilus

    EMBO Reports (2018) 19: e45543

    • Received November 24, 2017.
    • Revision received May 4, 2018.
    • Accepted May 8, 2018.
    Gediminas Drabavicius, Tomas Sinkunas, Arunas Silanskas, Giedrius Gasiunas, Česlovas Venclovas, Virginijus Siksnys
    Published online 11.06.2018
  • Open Access
    Dual role of USP30 in controlling basal pexophagy and mitophagy
    Dual role of USP30 in controlling basal pexophagy and mitophagy
    1. Elena Marcassa1,
    2. Andreas Kallinos1,
    3. Jane Jardine1,
    4. Emma V Rusilowicz‐Jones1,
    5. Aitor Martinez1,
    6. Sandra Kuehl2,
    7. Markus Islinger2,
    8. Michael J Clague (clague{at}liv.ac.uk)*,1 and
    9. Sylvie Urbé (urbe{at}liv.ac.uk)*,1
    1. 1Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
    2. 2Institute of Neuroanatomy, Centre for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
    1. ↵* Corresponding author. Tel: +44 151 7945308; E‐mail: clague{at}liv.ac.uk
      Corresponding author. Tel: +44 151 7945432; E‐mail: urbe{at}liv.ac.uk

    USP30 regulates basal mitophagy and its depletion unmasks a PINK1‐dependent component. USP30 is independently targeted to peroxisomes where it regulates PINK1‐independent basal pexophagy.

    Synopsis

    USP30 regulates basal mitophagy and its depletion unmasks a PINK1‐dependent component. USP30 is independently targeted to peroxisomes where it regulates PINK1‐independent basal pexophagy.

    • USP30 tonically suppresses basal mitophagy.

    • Basal mitophagy is independent of PINK1.

    • USP30 depletion reveals a PINK1‐dependent component of basal mitophagy.

    • USP30 is targeted to peroxisomes and suppresses basal pexophagy in a PINK1‐independent manner.

    • mitochondria
    • peroxisomes
    • PINK1
    • ubiquitin
    • mitophagy
    • USP30

    EMBO Reports (2018) 19: e45595

    • Received December 5, 2017.
    • Revision received May 15, 2018.
    • Accepted May 18, 2018.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Elena Marcassa, Andreas Kallinos, Jane Jardine, Emma V Rusilowicz‐Jones, Aitor Martinez, Sandra Kuehl, Markus Islinger, Michael J Clague, Sylvie Urbé
    Published online 12.06.2018
  • YAP and TAZ are essential for basal and squamous cell carcinoma initiation
    YAP and TAZ are essential for basal and squamous cell carcinoma initiation
    1. Maud Debaugnies1,†,
    2. Adriana Sánchez‐Danés1,†,
    3. Sandrine Rorive2,
    4. Maylis Raphaël1,
    5. Mélanie Liagre1,
    6. Marie‐Astrid Parent1,
    7. Audrey Brisebarre1,
    8. Isabelle Salmon2 and
    9. Cédric Blanpain (cedric.blanpain{at}ulb.ac.be)*,1,3
    1. 1Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles, Brussels, Belgium
    2. 2Department of Pathology, Erasme University Hospital, University Libre de Bruxelles, Brussels, Belgium
    3. 3WELBIO, Université Libre de Bruxelles, Brussels, Belgium
    1. ↵*Corresponding author. Tel: +32 2555 4175; E‐mail: cedric.blanpain{at}ulb.ac.be

    1. ↵† These authors contributed equally to this work

    The Hippo pathway transcription factors YAP and TAZ are expressed and active in basal and squamous cell carcinoma in mice and humans. Conditional deletion of YAP and TAZ in mouse models prevents skin cancer initiation.

    Synopsis

    The Hippo pathway transcription factors YAP and TAZ are expressed and active in basal and squamous cell carcinoma in mice and humans. Conditional deletion of YAP and TAZ in mouse models prevents skin cancer initiation.

    • YAP and TAZ are expressed in mouse and human basal and squamous cell carcinoma.

    • YAP and TAZ are mainly nuclear in basal and squamous cell carcinoma.

    • Basal and squamous cell carcinomas express YAP gene signatures.

    • Conditional deletion of YAP and TAZ prevents skin cancer initiation in mice.

    • basal cell carcinoma
    • cancer
    • squamous cell carcinoma
    • YAP
    • TAZ

    EMBO Reports (2018) 19: e45809

    • Received January 16, 2018.
    • Revision received May 4, 2018.
    • Accepted May 14, 2018.
    Maud Debaugnies, Adriana Sánchez‐Danés, Sandrine Rorive, Maylis Raphaël, Mélanie Liagre, Marie‐Astrid Parent, Audrey Brisebarre, Isabelle Salmon, Cédric Blanpain
    Published online 06.06.2018

Articles

  • Open Access
    Identification of MOSPD2, a novel scaffold for endoplasmic reticulum membrane contact sites
    Identification of MOSPD2, a novel scaffold for endoplasmic reticulum membrane contact sites
    1. Thomas Di Mattia1,2,3,4,
    2. Léa P Wilhelm1,2,3,4,
    3. Souade Ikhlef5,
    4. Corinne Wendling1,2,3,4,
    5. Danièle Spehner1,2,3,4,
    6. Yves Nominé1,2,3,4,
    7. Francesca Giordano6,
    8. Carole Mathelin1,2,3,4,7,
    9. Guillaume Drin5,
    10. Catherine Tomasetto (catherine-laure.tomasetto{at}igbmc.fr)*,1,2,3,4 and
    11. Fabien Alpy (fabien.alpy{at}igbmc.fr)*,1,2,3,4
    1. 1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France
    2. 2Institut National de la Santé et de la Recherche Médicale (INSERM), U1258, Illkirch, France
    3. 3Centre National de la Recherche Scientifique (CNRS), UMR7104, Illkirch, France
    4. 4Université de Strasbourg, Illkirch, France
    5. 5CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d'Azur, Valbonne, France
    6. 6Institut de Biologie Intégrative de la Cellule, CEA, CNRS, Paris‐Sud University Paris‐Saclay University, Gif‐sur‐Yvette Cedex 91198, France
    7. 7Senology Unit, Strasbourg University Hospital (CHRU), Hôpital de Hautepierre, Strasbourg, France
    1. ↵* Corresponding author. Tel: +33 3 88 65 34 24; Fax: +33 3 88 65 32 01; E‐mail: catherine-laure.tomasetto{at}igbmc.fr
      Corresponding author. Tel: +33 3 88 65 35 19; Fax: +33 3 88 65 32 01; E‐mail: fabien.alpy{at}igbmc.fr

    The endoplasmic reticulum (ER) makes physical contacts with most cellular organelles. This study identifies MOSPD2 as a new ER‐anchored receptor, which binds FFAT‐motif containing proteins in other organelles such as Golgi, endosomes and mitochondria.

    Synopsis

    The endoplasmic reticulum (ER) makes physical contacts with most cellular organelles. MOSPD2 (motile sperm domain‐containing protein 2) is a new ER‐anchored receptor, which binds FFAT (two phenylalanines in an acidic track)‐motif containing proteins. Analogous to vesicle‐associated membrane protein‐associated protein (VAP)‐A and VAP‐B, MOSPD2 mediates the formation of contact sites between the ER and a variety of organelles (including endosomes, mitochondria or Golgi).

    • Motile sperm domain‐containing protein 2 (MOSPD2) is a novel ER‐anchored VAP homolog.

    • The FFAT motif is recognized by the Major Sperm Protein (MSP) domain of MOSPD2.

    • MOSPD2 interacts with a variety of organelle (endosomes, mitochondria or Golgi)‐bound proteins and thereby builds membrane contact sites.

    • endoplasmic reticulum
    • ER–organelle contact
    • FFAT motif
    • membrane contact site
    • VAP proteins

    EMBO Reports (2018) 19: e45453

    • Received November 8, 2017.
    • Revision received April 27, 2018.
    • Accepted May 7, 2018.

    This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 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.

    Thomas Di Mattia, Léa P Wilhelm, Souade Ikhlef, Corinne Wendling, Danièle Spehner, Yves Nominé, Francesca Giordano, Carole Mathelin, Guillaume Drin, Catherine Tomasetto, Fabien Alpy
    Published online 01.06.2018
  • TG2 regulates the heat‐shock response by the post‐translational modification of HSF1
    TG2 regulates the heat‐shock response by the post‐translational modification of HSF1
    1. Federica Rossin1,
    2. Valeria Rachela Villella2,
    3. Manuela D'Eletto1,
    4. Maria Grazia Farrace1,
    5. Speranza Esposito2,
    6. Eleonora Ferrari2,
    7. Romina Monzani2,
    8. Luca Occhigrossi1,
    9. Vittoria Pagliarini3,4,
    10. Claudio Sette3,4,
    11. Giorgio Cozza5,
    12. Nikolai A Barlev6,
    13. Laura Falasca7,
    14. Gian Maria Fimia7,8,
    15. Guido Kroemer9,10,11,12,13,14,15,
    16. Valeria Raia16,
    17. Luigi Maiuri2,17 and
    18. Mauro Piacentini (mauro.piacentini{at}uniroma2.it)*,1,7
    1. 1Department of Biology, University of Rome ‘Tor Vergata’, Rome, Italy
    2. 2Division of Genetics and Cell Biology, European Institute for Research in Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy
    3. 3Department of Biomedicine and Prevention, University of Rome ‘Tor Vergata’, Rome, Italy
    4. 4Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy
    5. 5Department of Molecular Medicine, University of Padua, Padova, Italy
    6. 6Gene Expression Laboratory, Institute of Cytology, Saint‐Petersburg, Russia
    7. 7National Institute for Infectious Diseases IRCCS ‘L. Spallanzani’, Rome, Italy
    8. 8Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce, Italy
    9. 9Sorbonne Paris Cité, Université Paris Descartes, Paris, France
    10. 10Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France
    11. 11Institut National de la Santé et de la Recherche Médicale, U1138, Paris, France
    12. 12Université Pierre et Marie Curie, Paris, France
    13. 13Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
    14. 14Pôle de Biologie, Hôpital Européen Georges Pompidou, AP‐HP, Paris, France
    15. 15Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden
    16. 16Regional Cystic Fibrosis Center, Pediatric Unit, Department of Translational Medical Sciences, Federico II University, Naples, Italy
    17. 17SCDU of Pediatrics, Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
    1. ↵*Corresponding author. Tel: +39 0672 594234; E‐mail: mauro.piacentini{at}uniroma2.it

    TG2 triggers the trimerization and activation of HSF1 dependent on its disulphide isomerase activity. The inhibition of TG2 restores the unbalance in the HSF1‐HSP70 pathway in cystic fibrosis indicating a role for TG2 in the regulation of cellular proteostasis under stress.

    Synopsis

    TG2, through its protein disulphide isomerase activity, triggers the trimerization and activation of HSF1. The inhibition of TG2 restores the unbalance in HSF1‐HSP70 pathway in cystic fibrosis indicating that TG2 plays an important role in the regulation of cellular proteostasis under stressful cellular conditions through the modulation of the heat shock response.

    • The protein disulphide activity of TG2 post‐translationally modifies HSF1.

    • TG2, by activating HSF1, regulates HSP70 protein expression.

    • TG2 favour the degradation of mutant CFTR via the HSF1/HSP70 pathway.

    • Cystic fibrosis
    • HSF1
    • HSP70
    • proteostasis
    • TG2

    EMBO Reports (2018) 19: e45067

    • Received August 24, 2017.
    • Revision received March 24, 2018.
    • Accepted April 13, 2018.
    Federica Rossin, Valeria Rachela Villella, Manuela D'Eletto, Maria Grazia Farrace, Speranza Esposito, Eleonora Ferrari, Romina Monzani, Luca Occhigrossi, Vittoria Pagliarini, Claudio Sette, Giorgio Cozza, Nikolai A Barlev, Laura Falasca, Gian Maria Fimia, Guido Kroemer, Valeria Raia, Luigi Maiuri, Mauro Piacentini
    Published online 11.05.2018
  • Antagonistic interactions between two MAP kinase cascades in plant development and immune signaling
    Antagonistic interactions between two MAP kinase cascades in plant development and immune signaling
    1. Tongjun Sun1,†,
    2. Yukino Nitta1,†,
    3. Qian Zhang1,†,
    4. Di Wu1,
    5. Hainan Tian1,
    6. Jin Suk Lee2 and
    7. Yuelin Zhang (yuelin.zhang{at}ubc.ca)*,1
    1. 1Department of Botany, University of British Columbia, Vancouver, BC, Canada
    2. 2Department of Biology, Concordia University, Montreal, QC, Canada
    1. ↵*Corresponding author. Tel: +1 604 827 0076; E‐mail: yuelin.zhang{at}ubc.ca

    1. ↵† These authors contributed equally to this work

    MAPKKK3/5 act upstream of MKK4/5 and MPK3/6 in PAMP‐triggered and DAMP‐triggered immunity in plants. The MAPK pathways specified by MAPKKK3/5 and the developmental YDA pathway antagonize by competing for downstream MKKs.

    Synopsis

    MAPKKK3/5 act upstream of MKK4/5 and MPK3/6 in PAMP‐triggered and DAMP‐triggered immunity in plants. The MAPK pathways specified by MAPKKK3/5 and the developmental YDA pathway antagonize by competing for downstream MKKs.

    • MAPKKK3/5, MKK4/5 and MPK3/6 form a MAPK cascade to transduce defence signals in PTI.

    • Developmental defects caused by silencing YDA are suppressed in the mapkkk3/5 double mutant.

    • Loss of YDA leads to increased PAMP‐induced activation of MPK3/MPK6.

    • Brassinosteroid has an inhibitory effect on PAMP‐induced MAPK activation.

    • MAPK signaling
    • MAPKKK3
    • MAPKKK5
    • PAMP‐triggered immunity
    • YODA/YDA

    EMBO Reports (2018) 19: e45324

    • Received October 12, 2017.
    • Revision received April 21, 2018.
    • Accepted April 25, 2018.
    Tongjun Sun, Yukino Nitta, Qian Zhang, Di Wu, Hainan Tian, Jin Suk Lee, Yuelin Zhang
    Published online 22.05.2018
  • Aβ1–42 triggers the generation of a retrograde signaling complex from sentinel mRNAs in axons
    Aβ<sub>1–42</sub> triggers the generation of a retrograde signaling complex from sentinel mRNAs in axons
    1. Chandler A Walker1,
    2. Lisa K Randolph2,
    3. Carlos Matute3,4,5,
    4. Elena Alberdi3,4,5,
    5. Jimena Baleriola3,6,7 and
    6. Ulrich Hengst (uh2112{at}cumc.columbia.edu)*,7,8
    1. 1Integrated Program in Cellular, Molecular and Biomedical Studies, Columbia University Irving Medical Center, New York, NY, USA
    2. 2Doctoral Program in Neurobiology and Behavior, Columbia University, New York, NY, USA
    3. 3Achucarro Basque Center for Neuroscience, Leioa, Spain
    4. 4Departamento de Neurociencias, Universidad del País Vasco (UPV/EHU), Leioa, Spain
    5. 5Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED), Leioa, Spain
    6. 6IKERBASQUE Basque Foundation for Science, Bilbao, Spain
    7. 7The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA
    8. 8Department of Pathology & Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
    1. ↵*Corresponding author. Tel: +1 212 305 9334; E‐mail: uh2112{at}cumc.columbia.edu

    Aβ1–42 triggers translation of axonal mRNAs whose protein products form signaling complexes that transmit the presence of Aβ1–42 from the cellular periphery back to the neuronal soma.

    Synopsis

    Aβ1–42 triggers translation of axonal mRNAs whose protein products form signaling complexes that transmit the presence of Aβ1–42 from the cellular periphery back to the neuronal soma.

    • Translation of pre‐localized sentinel mRNAs is an immediate response mechanism of axons to Aβ1–42.

    • Axonal protein synthesis generates a retrograde signaling complex that transmits the information regarding the insult to the cell body.

    • Axonal production of vimentin is required for the retrograde signaling complex.

    • Alzheimer's disease
    • axonal protein synthesis
    • neurodegeneration
    • oligomeric Aβ1–42
    • retrograde signal

    EMBO Reports (2018) 19: e45435

    • Received November 3, 2017.
    • Revision received April 20, 2018.
    • Accepted April 24, 2018.
    Chandler A Walker, Lisa K Randolph, Carlos Matute, Elena Alberdi, Jimena Baleriola, Ulrich Hengst
    Published online 14.05.2018
  • Map7/7D1 and Dvl form a feedback loop that facilitates microtubule remodeling and Wnt5a signaling
    Map7/7D1 and Dvl form a feedback loop that facilitates microtubule remodeling and Wnt5a signaling
    1. Koji Kikuchi (kojik{at}kumamoto-u.ac.jp)*,1,
    2. Akira Nakamura2,3,
    3. Masaki Arata4,
    4. Dongbo Shi5,
    5. Mami Nakagawa5,
    6. Tsubasa Tanaka2,3,
    7. Tadashi Uemura4,
    8. Toshihiko Fujimori5,
    9. Akira Kikuchi6,
    10. Akiyoshi Uezu1,
    11. Yasuhisa Sakamoto1 and
    12. Hiroyuki Nakanishi (hnakanis{at}gpo.kumamoto-u.ac.jp)*,1
    1. 1Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kumamoto University, Chuo‐ku Kumamoto, Japan
    2. 2Department of Germline Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Chuo‐ku Kumamoto, Japan
    3. 3Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo‐ku Kumamoto, Japan
    4. 4Graduate School of Biostudies, Kyoto University, Sakyo‐ku Kyoto, Japan
    5. 5Division of Embryology, National Institute for Basic Biology, Okazaki Aichi, Japan
    6. 6Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita Osaka, Japan
    1. ↵* Corresponding author (Lead contact): +Tel: +81 96 373 5076; E‐mail: kojik{at}kumamoto-u.ac.jp
      Corresponding author. +Tel: +81 96 373 5074; E‐mail: hnakanis{at}gpo.kumamoto-u.ac.jp

    Microtubule‐associated proteins Map7/7D1/Ensconsin and Dishevelled form an evolutionarily conserved axis in β‐catenin‐independent Wnt signaling and/or PCP formation.

    Synopsis

    Microtubule‐associated proteins Map7/7D1/Ens and Dishevelled form an evolutionarily conserved axis in β‐catenin‐independent Wnt signaling and/or PCP formation.

    • Map7/7D1 cooperate with a Kinesin‐1 Kif5b to coordinate Dishevelled dynamics and microtubule remodeling in the Wnt5a signaling pathway.

    • Map7/7D1 and their fly homolog Ens show planar‐polarized distribution in both mouse and fly epithelia.

    • Ens is required for polarized localization of Dishevelled during PCP formation in pupal wing epithelia.

    • Map7/7D1/Ens play an evolutionarily conserved role in Dishevelled localization.

    • Disheveled
    • Kinesin‐1
    • microtubule remodeling
    • microtubule‐associated proteins
    • β‐catenin‐independent Wnt5a signaling

    EMBO Reports (2018) 19: e45471

    • Received November 9, 2017.
    • Revision received April 28, 2018.
    • Accepted May 8, 2018.
    Koji Kikuchi, Akira Nakamura, Masaki Arata, Dongbo Shi, Mami Nakagawa, Tsubasa Tanaka, Tadashi Uemura, Toshihiko Fujimori, Akira Kikuchi, Akiyoshi Uezu, Yasuhisa Sakamoto, Hiroyuki Nakanishi
    Published online 07.06.2018
  • Tel1/ATM prevents degradation of replication forks that reverse after topoisomerase poisoning
    Tel1/ATM prevents degradation of replication forks that reverse after topoisomerase poisoning
    1. Luca Menin1,
    2. Sebastian Ursich2,
    3. Camilla Trovesi1,3,
    4. Ralph Zellweger2,
    5. Massimo Lopes2,
    6. Maria Pia Longhese (mariapia.longhese{at}unimib.it)*,1 and
    7. Michela Clerici (michela.clerici{at}unimib.it)*,1
    1. 1Dipartimento di Biotecnologie e Bioscienze, Università di Milano‐Bicocca, Milano, Italy
    2. 2Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
    3. 3Present Address: Istituto Nazionale di Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milano, Italy
    1. ↵* Corresponding author. Tel: +39 0264483425; Fax: +39 0264483565; E‐mail: mariapia.longhese{at}unimib.it
      Corresponding author. Tel: +39 0264483547; Fax: +39 0264483565; E‐mail: michela.clerici{at}unimib.it

    The topoisomerase poison camptothecin (CPT) induces fork reversal, which is thought to stabilize replication forks. Here, yeast Tel1, orthologue of human ATM, protects CPT‐induced reversed forks from nucleolytic degradation by the MRX complex.

    Synopsis

    The topoisomerase poison camptothecin (CPT) induces fork reversal, which is thought to stabilize replication forks. Here, yeast Tel1, orthologue of human ATM, protects CPT‐induced reversed forks from nucleolytic degradation by the MRX complex.

    • The absence of Tel1 or its kinase activity causes a specific hypersensitivity to CPT and decreases fork reversal in CPT.

    • The decreased reversed fork levels in the absence of Tel1 are due to unscheduled nucleolytic processing that depends mainly on Mre11 nuclease activity.

    • Tel1 function in reversed fork stabilization becomes dispensable when fork reversal is prevented by the lack of the replisome‐associated factor Mrc1, whose absence also relieves the hypersensitivity to CPT of tel1Δ cells.

    • camptothecin
    • fork reversal
    • Mrc1
    • MRX
    • Tel1

    EMBO Reports (2018) 19: e45535

    • Received November 23, 2017.
    • Revision received April 12, 2018.
    • Accepted April 19, 2018.
    Luca Menin, Sebastian Ursich, Camilla Trovesi, Ralph Zellweger, Massimo Lopes, Maria Pia Longhese, Michela Clerici
    Published online 08.05.2018
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Volume 19, Number 7
01 July 2018
EMBO reports: 19 (7)
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