Table of Contents
01 July 2017; volume 18, issue 7
News & Views
- Let's burn whatever you have: mitofusin 2 metabolically re‐wires brown adipose tissue
Brown adipose tissue (BAT) has received enormous scientific and lay attention in the recent past as its thermogenic, energy‐consuming capacities represent prime candidates for therapeutic interventions toward obesity, glucose intolerance, and diabetes even in humans. The overall positive effects of BAT activation and recruitment on systemic energy homeostasis have been largely attributed to the inherent ability of brown adipocytes to combust fatty acid and glucose energy substrates through mitochondrial uncoupling, driven by the unique expression of uncoupling protein 1 (UCP1). Two recent reports by Boutant et al and Mahdaviani et al now identify the GTPase mitofusin (Mfn) 2 as a key determinant of BAT thermogenic function that is largely independent of its previously described role in mitochondrial fusion [1,2].
See also: K Mahdaviani et al (July 2017) and M Boutant et al (June 2017)
Two studies in EMBO Reports and The EMBO Journal identify the GTPase mitofusin 2 as critical determinant of brown adipocyte tissue thermogenic function and insulin sensitivity.
- © 2017 The Authors
- ATP synthase complex and the mitochondrial permeability transition pore: poles of attraction
- Christos Chinopoulos (chinopoulos.christos{at}eok.sote.hu)1
The identity of the mitochondrial permeability transition (mPT) pore, a megachannel embedded in the inner membrane opened by Ca2+, is fiercely debated. Unraveling the components structuring this pore is critical for combating diseases as diverse as neurodegeneration, cancer, autoimmunity, and myopathies in which this phenomenon is implicated. Current consensus is that the pore is formed within, or in‐between F0F1 ATP synthase dimers, but not through their c‐subunit ring. Two recent studies in this issue of EMBO Reports throw more light on these aspects, one by Giorgio et al [1] showing that the β subunit of the ATP synthase harbors a Ca2+‐binding site responsible for triggering mPT, and the other by Bonora et al [2] demonstrating that permeability transition requires dissociation of F0F1 ATP synthase dimers, albeit in a manner involving the c‐subunit ring.
See also: V Giorgio et al (July 2017) and
M Bonora et al (July 2017)
Two studies in this issue shed light on the mechanism of mitochondrial permeability transition pore formation by the F‐ATPase and pore opening by calcium sensing and dimer dissociation.
- © 2017 The Author
- Enzyme sub‐functionalization driven by regulation
The emergence of functional novelties during protein evolution has puzzled scientists for many years. Most proposed models focus on repeated duplication‐divergence cycles, but the entanglement of selection pressures acting on the control of transcriptional and enzymatic activity, for example, by metabolites, has not been addressed so far. In this issue of EMBO Reports, Noda‐Garcia et al [1] describe two glutamate dehydrogenase paralogs from Bacillus subtilis with very similar sequences and under two distinct modes of activity control. The functional divergence of these two enzymes during evolution is driven by an interlinked combination of differences between their enzymatic properties and their transcriptional regulation. This article thus illuminates another level of complexity in molecular evolution that may help understand the hitherto unexplained co‐existence of paralogous genes that at first sight appear to be functionally redundant.
See also: L Noda‐Garcia et al (July 2017)
A study in this issue shows how the co‐evolution of transcriptional and enzyme activity regulation contributes to the functional divergence of two Bacilli glutamate dehydrogenase paralogs.
- © 2017 The Authors
Correspondence
- Comment on “How we become ill” by Patrick Finzer
- Agnese Mariotti, Freelance science writer (amariotti9g{at}gmail.com)1
A comment on “How we become ill” by Patrick Finzer.
- © 2017 The Author
Science & Society
- Inventive steps: the CRISPR patent dispute and scientific progressThe recent patent decisions about CRISPR tell us a lot about how advances in biology are actually made—and how they are not
The recent patent decisions about CRISPR tell us a lot about how advances in biology are actually made—and how they are not
- Jacob S Sherkow (jacob.sherkow{at}nyls.edu)1
Inventions in scientific research and inventions under patent law do not necessarily mean the same—in particular in molecular biology.
- © 2017 The Author
- Taking distrust of science seriouslyTo overcome public distrust in science, scientists need to stop pretending that there is a scientific consensus on controversial issues when there is not
To overcome public distrust in science, scientists need to stop pretending that there is a scientific consensus on controversial issues when there is not
- Geoffrey C Kabat (geoffrey.kabat{at}einstein.yu.edu)1
Scientific disputes on controversial issues – from endocrine disrupting chemicals to climate change – risk increasing public distrust in science if scientists pretend that there is a consensus when in fact there is not.
- © 2017 The Author
- The “Anthropocene”: neglects, misconceptions, and possible futuresThe term “Anthropocene” is often erroneously used, as it is not formally defined yet
The term “Anthropocene” is often erroneously used, as it is not formally defined yet
- Valentí Rull (vrull{at}ictja.csic.es)1
Despite its popularity in scientific and social media, the “Anthropocene” is a term and concept still under discussion and still not formally recognized as a new geologic epoch.
- © 2017 The Author
- The long‐term health risks of ARTEpidemiological data and research on animals indicate that in vitro fertilization might create health problems later in life
Epidemiological data and research on animals indicate that in vitro fertilization might create health problems later in life
- Philip Hunter, Freelance journalist (ph{at}philiphunter.com)1
Since the birth of Louise Brown 39 years ago, scientists have been suspecting that assisted reproductive technologies could create long‐term health risks. While evidence remains inconclusive, ongoing research and improvements help to reduce such risks.
- © 2017 The Author
Scientific Reports
- Ca2+ binding to F‐ATP synthase β subunit triggers the mitochondrial permeability transition
- Valentina Giorgio (vgiorgio{at}bio.unipd.it)*,1,2,†,
- Victoria Burchell1,†,
- Marco Schiavone1,
- Claudio Bassot1,
- Giovanni Minervini1,
- Valeria Petronilli1,2,
- Francesco Argenton3,
- Michael Forte4,
- Silvio Tosatto1,2,
- Giovanna Lippe (giovanna.lippe{at}uniud.it)*,5 and
- Paolo Bernardi (bernardi{at}bio.unipd.it)*,1,2
- 1Department of Biomedical Sciences, University of Padova, Padova, Italy
- 2Consiglio Nazionale delle Ricerche Neuroscience Institute, Padova, Italy
- 3Department of Biology, University of Padova, Padova, Italy
- 4Vollum Institute, Oregon Health and Sciences University, Portland, OR, USA
- 5Department of Agricultural, Food, Environmental and Animal Sciences, University of Udine, Udine, Italy
- ↵*
Corresponding author. Tel: +39 04982 76361; E‐mail: vgiorgio{at}bio.unipd.it
Corresponding author. Tel: +39 04325 58139; E‐mail: giovanna.lippe{at}uniud.it
Corresponding author. Tel: +39 04982 76365; E‐mail: bernardi{at}bio.unipd.it
↵† These authors contributed equally to this work
In response to Ca2+ ions mitochondria can undergo a permeability transition (PT). This study provides evidence that Ca2+‐binding to the catalytic β subunit of F1F0 ATPase induces a conformational change that triggers pore opening.
Synopsis
In response to Ca2+ ions mitochondria can undergo a permeability transition (PT). This study provides evidence that Ca2+‐binding to the catalytic β subunit of F1F0 ATPase induces a conformational change that is transduced to the OSCP subunit and the lateral stalk to induce pore opening.
Onset of the PT depends on Ca2+ binding to T163 of F‐ATP synthase β subunit, which in physiological catalysis coordinates Mg2+.
Ca2+ binding to the catalytic site may induce a conformational change that is transmitted to the peripheral stalk through OSCP, leading to the PT.
A T163S mutation increases Mg2+‐ATPase and inhibits Ca2+‐ATPase activity, prevents PT‐dependent HeLa cells death and lowers incidence of apoptosis in developing zebrafish embryos.
EMBO Reports (2017) 18: 1065–1076
- Received September 15, 2016.
- Revision received April 2, 2017.
- Accepted April 5, 2017.
- © 2017 The Authors
- Mitochondrial permeability transition involves dissociation of F1FO ATP synthase dimers and C‐ring conformation
- Massimo Bonora1,2,
- Claudia Morganti1,2,
- Giampaolo Morciano1,2,
- Gaia Pedriali1,2,
- Magdalena Lebiedzinska‐Arciszewska3,
- Giorgio Aquila4,
- Carlotta Giorgi1,2,
- Paola Rizzo4,
- Gianluca Campo5,
- Roberto Ferrari5,
- Guido Kroemer6,7,8,9,10,11,12,
- Mariusz R Wieckowski (m.wieckowski{at}nencki.gov.pl)*,3,
- Lorenzo Galluzzi (deadoc{at}vodafone.it)*,6,13 and
- Paolo Pinton (paolo.pinton{at}unife.it)*,1,2
- 1Department of Morphology, Surgery and Experimental Medicine, Section of General Pathology, University of Ferrara, Ferrara, Italy
- 2Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy
- 3Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland
- 4Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
- 5Cardiovascular Institute, University of Ferrara, Ferrara, Italy
- 6Université Paris Descartes/Paris V, Paris, France
- 7Université Pierre et Marie Curie/Paris VI, Paris, France
- 8INSERM, U1138, Paris, France
- 9Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France
- 10Pôle de Biologie, Hôpital Européen Georges Pompidou, AP‐HP, Paris, France
- 11Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
- 12Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden
- 13Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
- ↵*
Corresponding author. Tel: +48 22 5892372; E‐mail: m.wieckowski{at}nencki.gov.pl
Corresponding author. Tel: +1 212 746 2231; E‐mail: deadoc{at}vodafone.it
Corresponding author. Tel: +39 0532 455802; E‐mail: paolo.pinton{at}unife.it
F1FO ATP synthase dimer dissociation plays a crucial role in MPT and allows PTPC opening. In the same context, c subunit‐specific mutations altering the C‐ring conformation prime cells for MPT induction.
Synopsis
F1FO ATP synthase dimer dissociation plays a crucial role in MPT and allows PTPC opening. In the same context, c subunit‐specific mutations altering the C‐ring conformation prime cells for MPT induction.
MPT is linked with dissociation of F1FO ATP synthase dimers and their stabilization by ATPIF1 or ATP5I overexpression inhibits PTPC opening.
The glycine zipper domain of the c subunit plays a central role in the MPT process as specific mutations promoting conformational changes in the C‐ring structure affect PTPC opening.
A proper C‐ring conformation is required for MPT induction once F1FO ATP synthase dimers have dissociated.
EMBO Reports (2017) 18: 1077–1089
- Received October 31, 2016.
- Revision received April 22, 2017.
- Accepted April 25, 2017.
- © 2017 The Authors
- In vivo structures of an intact type VI secretion system revealed by electron cryotomography
- 1California Institute of Technology, Pasadena, CA, USA
- 2Howard Hughes Medical Institute, Pasadena, CA, USA
- ↵*Corresponding author. Tel: +1 626 3958827; E‐mail: jensen{at}caltech.edu
Bacterial type VI secretion systems are molecular weapons used against eukaryotic hosts or prokaryotic competitors. This study presents the in situ architecture of the complete Myxococcus xanthus T6SS and the structures of several poorly characterized components.
Synopsis
Bacterial type VI secretion systems are molecular weapons used against eukaryotic hosts or prokaryotic competitors. This study presents the in situ architecture of the complete Myxococcus xanthus T6SS and the structures of several poorly characterized components.
Structure of the extended T6SS sheath and location of the recycling domains.
Structure of the baseplate and membrane complex in vivo.
Discovery of extracellular antennae likely involved in target recognition.
EMBO Reports (2017) 18: 1090–1099
- Received February 13, 2017.
- Revision received March 16, 2017.
- Accepted April 5, 2017.
- © 2017 The Authors
- The signaling lipid phosphatidylinositol‐3,5‐bisphosphate targets plant CLC‐a anion/H+ exchange activity
- Armando Carpaneto1,
- Anna Boccaccio1,
- Laura Lagostena1,
- Eleonora Di Zanni1 and
- Joachim Scholz‐Starke (joachim.scholzstarke{at}ge.ibf.cnr.it)*,1
- ↵*Corresponding author. Tel: +39 010 6475593; Fax: +39 010 6475500; E‐mail: joachim.scholzstarke{at}ge.ibf.cnr.it
This study identifies inhibition of CLC‐a dependent anion/H+ exchange as a vacuolar target of the signaling lipid phosphatidylinositol‐3,5‐bisphosphate. This provides a clue to the lipid's positive effect on vacuolar acidification in plant cells.
Synopsis
This study identifies inhibition of CLC‐a dependent anion/H+ exchange as a vacuolar target of the signaling lipid phosphatidylinositol‐3,5‐bisphosphate. This provides a clue to the lipid's positive effect on vacuolar acidification in plant cells.
PI(3,5)P2 does not affect major vacuolar H+ pump activities.
Vacuolar acidification elicited by prolonged H+ pumping activity revealed a novel H+‐dependent chloride conductance mediated by the anion/H+ exchanger CLC‐a.
CLC‐a anion/H+ exchange activity is reversibly inhibited by PI(3,5)P2 at low nanomolar concentrations.
CLC‐a inhibition contributes to vacuolar acidification.
EMBO Reports (2017) 18: 1100–1107
- Received December 14, 2016.
- Revision received April 20, 2017.
- Accepted April 21, 2017.
- © 2017 The Authors
Articles
- Brd4‐Brd2 isoform switching coordinates pluripotent exit and Smad2‐dependent lineage specification
- Rosalia Fernandez‐Alonso1,
- Lindsay Davidson2,
- Jens Hukelmann3,
- Michael Zengerle4,
- Alan R Prescott3,
- Angus Lamond3,
- Alessio Ciulli4,
- Gopal P Sapkota1 and
- Greg M Findlay (g.m.findlay{at}dundee.ac.uk)*,1
- 1The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, The University of Dundee, Dundee, UK
- 2Pluripotent Stem Cell Facility, School of Life Sciences, The University of Dundee, Dundee, UK
- 3Centre for Gene Regulation and Expression, School of Life Sciences, The University of Dundee, Dundee, UK
- 4Biological Chemistry and Drug Discovery, School of Life Sciences, The University of Dundee, Dundee, UK
- ↵*Corresponding author. Tel: +44 1382 386066; E‐mail: g.m.findlay{at}dundee.ac.uk
BET bromodomain proteins are key regulators of Nodal‐Smad2 signalling during mesendoderm differentiation of mESCs. In this system distinct functionalities of the BET family proteins Brd2 and Brd4 coordinate the exit from pluripotency with mesendoderm specification.
Synopsis
BET bromodomain proteins are key regulators of Nodal‐Smad2 signalling during mesendoderm differentiation of mESCs. In this system distinct functionalities of the BET family proteins Brd2 and Brd4 coordinate the exit from pluripotency with mesendoderm specification.
BET bromodomain activity regulates the Nodal‐Smad2 pathway and mesendoderm specification.
Brd2‐Brd4 recruitment controls Nodal expression and Smad2 signalling in differentiating mESCs.
Distinct Brd2‐Brd4 roles ensure that pluripotent exit coordinates with mesendoderm specification.
Brd2 is a novel specific regulator of Nodal‐Smad2 signalling and mesendoderm differentiation.
EMBO Reports (2017) 18: 1108–1122
- Received October 18, 2016.
- Revision received April 15, 2017.
- Accepted April 24, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
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.
- Mfn2 deletion in brown adipose tissue protects from insulin resistance and impairs thermogenesis
- Kiana Mahdaviani1,2,
- Ilan Y Benador1,2,
- Shi Su1,
- Raffi A Gharakhanian1,
- Linsey Stiles1,2,
- Kyle M Trudeau1,2,
- Maria Cardamone3,
- Violeta Enríquez‐Zarralanga1,
- Eleni Ritou1,2,
- Tamar Aprahamian4,
- Marcus F Oliveira1,5,
- Barbara E Corkey1,
- Valentina Perissi3,
- Marc Liesa (mliesa{at}mednet.ucla.edu)*,1,2 and
- Orian S Shirihai (oshirihai{at}mednet.ucla.edu)*,1,2,6
- 1Obesity Research Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
- 2Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- 3Biochemistry Department, Boston University School of Medicine, Boston, MA, USA
- 4Renal Section, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
- 5Laboratório de Bioquímica de Resposta ao Estresse, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
- 6Department of Clinical Biochemistry, School of Medicine, Ben Gurion University, Beer‐Sheva, Israel
- ↵*
Corresponding author. Tel: +1 310‐206‐7319; E‐mail: mliesa{at}mednet.ucla.edu
Corresponding author. Tel: +1 617 230 8570; E‐mail: oshirihai{at}mednet.ucla.edu
Deletion of Mfn2 in BAT improves glucose tolerance under high fat diet while impairing cold‐induced thermogenesis. Therefore, BAT therapeutic potential to improve insulin sensitivity may be achieved independently of thermogenesis.
Synopsis
Deletion of Mfn2 in BAT improves glucose tolerance under high fat diet while impairing cold‐induced thermogenesis. Therefore, BAT therapeutic potential to improve insulin sensitivity may be achieved independently of thermogenesis.
Mfn2 in BAT is required to sustain body temperature after cold‐exposure.
Mfn2 deletion in BAT protects from obesity‐induced insulin resistance and increases whole body lipid oxidation.
In obesity, Mfn2 deletion in BAT promotes a gender‐specific remodeling of BAT mitochondria and metabolism to increase ATP synthesis capacity.
EMBO Reports (2017) 18: 1123–1138
- Received December 15, 2016.
- Revision received April 3, 2017.
- Accepted April 10, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
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.
- Bacilli glutamate dehydrogenases diverged via coevolution of transcription and enzyme regulation
- Lianet Noda‐Garcia1,
- Maria Luisa Romero Romero1,
- Liam M Longo1,
- Ilana Kolodkin‐Gal2 and
- Dan S Tawfik (dan.tawfik{at}weizmann.ac.il)*,1
- 1Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel
- 2Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
- ↵*Corresponding author. Tel: +972 8 934 3637; E‐mail: dan.tawfik{at}weizmann.ac.il
Bacilli have two glutamate dehydrogenase paralogues. Regulation has diverged from transcriptional control in one paralogue (RocG) to enzyme control in the other (GudB), thus creating incompatibility upon swaps of enzymes and regulatory regions.
Synopsis
Bacilli have two glutamate dehydrogenase paralogues. Regulation has diverged from transcriptional control in one paralogue (RocG) to enzyme control in the other (GudB), thus creating incompatibility upon swaps of enzymes and regulatory regions (promoter/terminator).
Swapping enzymes and regulatory regions of the Bacilli glutamate dehydrogenase paralogues reveals coevolution of transcription and enzyme regulation.
Coevolution of transcriptional and enzymatic regulation underlies paralogue‐specific spatio‐temporal control.
The Bacilli glutamate dehydrogenases are regulated via oligomer assembly.
EMBO Reports (2017) 18: 1139–1149
- Received January 25, 2017.
- Revision received March 23, 2017.
- Accepted March 27, 2017.
- © 2017 The Authors
- Lipophagy prevents activity‐dependent neurodegeneration due to dihydroceramide accumulation in vivo
- Wei‐Hung Jung1,†,
- Chung‐Chih Liu1,†,
- Yu‐Lian Yu1,
- Yu‐Chin Chang1,
- Wen‐Yu Lien1,
- Hsi‐Chun Chao2,
- Shu‐Yi Huang3,
- Ching‐Hua Kuo2,
- Han‐Chen Ho4 and
- Chih‐Chiang Chan (chancc1{at}ntu.edu.tw)*,1
- 1Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan
- 2School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
- 3Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
- 4Department of Anatomy, Tzu‐Chi University, Hualien, Taiwan
- ↵*Corresponding author. Tel: +886 223123456 88240; E‐mail chancc1{at}ntu.edu.tw
↵† These authors contributed equally to this work
This study dissects the role of the fly dhCer desaturase ifc in neurons by genetic and pharmaceutical methods. dhCer desaturase is required for neuronal maintenance in vivo and lipophagy activation prevents activity‐dependent degeneration due to dhCer accumulation.
Synopsis
This study dissects the role of the fly dhCer desaturase ifc in neurons by genetic and pharmaceutical methods. dhCer desaturase is required for neuronal maintenance in vivo and lipophagy activation prevents activity‐dependent degeneration due to dhCer accumulation.
Light stimulation leads to ROS increase and apoptotic cell death in ifc‐KO photoreceptors, resulting in activity‐dependent neurodegeneration.
Enhancing lipophagy reduces lipid droplet accumulation and rescues ifc‐KO defects, indicating that lipophagy plays a protective role.
Human dhCer desaturase rescues ifc‐KO larval lethality in Drosophila and rapamycin reverses defects caused by dhCer accumulation in human neuroblastoma cells, suggesting evolutionarily conserved functions.
EMBO Reports (2017) 18: 1150–1165
- Received October 7, 2016.
- Revision received March 30, 2017.
- Accepted April 6, 2017.
- © 2017 The Authors
- Salt‐inducible kinase induces cytoplasmic histone deacetylase 4 to promote vascular calcification
- Alon Abend1,
- Omer Shkedi1,
- Michal Fertouk1,2,
- Lilac H Caspi1 and
- Izhak Kehat (ikehat{at}tx.technion.ac.il)*,1,3
- 1The Rappaport Institute and the Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
- 2Department of Cardiac Surgery, Rambam Medical Center, Haifa, Israel
- 3Department of Cardiology and the Clinical Research Institute at Rambam, Rambam Medical Center, Haifa, Israel
- ↵*Corresponding author. Tel/fax: +972 4 8295378; E‐mail: ikehat{at}tx.technion.ac.il
HDAC4 is upregulated in vascular smooth muscle cells during vascular calcification. Salt inducible kinase triggers HDAC4's cytoplasmic localization, and cytoplasmic HDAC4 together with ENIGMA drives vascular calcification.
Synopsis
HDAC4 is upregulated in vascular smooth muscle cells during vascular calcification. Salt inducible kinase triggers HDAC4's cytoplasmic localization, and cytoplasmic HDAC4 together with ENIGMA drives vascular calcification.
The cytoplasmic location and function of HDAC4 is controlled by the activity of salt inducible kinase (SIK).
Pharmacologic inhibition of SIK sends HDAC4 to the nucleus and inhibits the calcification process.
In the cytoplasm, HDAC4 binds to and its activity depends on the cytoskeletal adaptor protein ENIGMA (Pdlim7).
EMBO Reports (2017) 18: 1166–1185
- Received November 17, 2016.
- Revision received April 18, 2017.
- Accepted April 26, 2017.
- © 2017 The Authors
- TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury
- Fargol Mazaheri1,
- Nicolas Snaidero2,3,
- Gernot Kleinberger4,5,
- Charlotte Madore6,
- Anna Daria5,
- Georg Werner5,
- Susanne Krasemann7,
- Anja Capell5,
- Dietrich Trümbach8,
- Wolfgang Wurst1,4,8,9,
- Bettina Brunner1,
- Sebastian Bultmann10,
- Sabina Tahirovic1,
- Martin Kerschensteiner3,4,
- Thomas Misgeld1,2,4,
- Oleg Butovsky6 and
- Christian Haass (christian.haass{at}mail03.med.uni-muenchen.de)*,1,4,5
- 1German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany
- 2Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany
- 3Institute for Clinical Neuroimmunology, Biomedical Center (BMC) and University Hospital, Ludwig‐Maximilians‐Universität München, Munich, Germany
- 4Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
- 5Biomedical Center (BMC), Biochemistry, Ludwig‐Maximilians Universität München, Munich, Germany
- 6Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- 7Institute for Neuropathology, University Medical Center Hamburg‐Eppendorf, Hamburg, Germany
- 8Institute of Developmental Genetics, Helmholtz Zentrum München, Neuherberg, Germany
- 9Developmental Genetics, Technical University Munich‐Weihenstephan, Neuherberg, Germany
- 10Department of Biology and Center for Integrated Protein Science Munich (CIPSM), Ludwig Maximilians‐Universität München, Munich, Germany
- ↵*Corresponding author. Tel: +49 89 4400 46549; E‐mail: christian.haass{at}mail03.med.uni-muenchen.de
TREM2 sequence variations are linked to neurodegenerative disorders. Transcriptomic and functional studies show that TREM2‐deficient microglia display a homeostatic mRNA signature and are impaired in chemotaxis and their response to neuronal injury.
Synopsis
TREM2 sequence variations are linked to neurodegenerative disorders. Transcriptomic and functional studies show that TREM2‐deficient microglia display a homeostatic mRNA signature and are impaired in chemotaxis and their response to neuronal injury.
TREM2 deficiency in microglia affects expression profiles of gene clusters involved in chemotaxis.
TREM2 deficiency impairs migration, chemotaxis and process outgrowth.
TREM2‐deficient microglia display a homeostatic mRNA signature.
EMBO Reports (2017) 18: 1186–1198
- Received January 10, 2017.
- Revision received March 27, 2017.
- Accepted March 31, 2017.
- © 2017 The Authors
- Circadian networks in human embryonic stem cell‐derived cardiomyocytes
- Pieterjan Dierickx (p.dierickx{at}hubrecht.eu)*,1,2,3,
- Marit W Vermunt1,
- Mauro J Muraro1,
- Menno P Creyghton1,
- Pieter A Doevendans2,4,
- Alexander van Oudenaarden1,
- Niels Geijsen1,† and
- Linda W Van Laake (l.w.vanlaake{at}umcutrecht.nl)*,2,3,†
- 1Hubrecht Institute‐KNAW and University Medical Center Utrecht, Utrecht, The Netherlands
- 2Division of Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
- 3Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands
- 4Netherlands Heart Institute, Utrecht, The Netherlands
- ↵*
Corresponding author. Tel: +31 302121800; E‐mail: p.dierickx{at}hubrecht.eu
Corresponding author. Tel: +31 887555555; E‐mail: l.w.vanlaake{at}umcutrecht.nl
↵† These authors contributed equally to this work
The circadian clock is important for proper heart function. This study describes the functional implications of the gradual emergence of a clock during directed cardiac differentiation of human embryonic stem cells.
Synopsis
The circadian clock is important for proper heart function. This study describes the functional implications of the gradual emergence of a clock during directed cardiac differentiation of human embryonic stem cells.
Human embryonic stem cells do not have a functional circadian clock.
A functional circadian clock emerges during directed cardiac differentiation.
Stem cell‐derived cardiomyocytes possess an oscillatory stress‐related transcriptional network.
Stem cell‐derived cardiomyocytes respond to doxorubicin in a time‐dependent circadian pattern.
EMBO Reports (2017) 18: 1199–1212
- Received January 3, 2017.
- Revision received March 29, 2017.
- Accepted April 10, 2017.
- © 2017 The Authors. Published under the terms of the CC BY NC ND 4.0 license
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.
- Synergistic action of auxin and cytokinin mediates aluminum‐induced root growth inhibition in Arabidopsis
- Zhong‐Bao Yang1,†,
- Guangchao Liu1,†,
- Jiajia Liu1,
- Bing Zhang1,
- Wenjing Meng2,
- Bruno Müller3,
- Ken‐ichiro Hayashi4,
- Xiansheng Zhang2,
- Zhong Zhao5,
- Ive De Smet6,7 and
- Zhaojun Ding (dingzhaojun{at}sdu.edu.cn)*,1
- 1The Key Laboratory of Plant Cell Engineering and Germplasm Innovation, Ministry of Education, College of Life Science, Shandong University, Jinan, China
- 2State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Taian, China
- 3Institute of Plant Biology, University of Zurich, Zurich, Switzerland
- 4Department of Biochemistry, Okayama University of Science, Okayama, Japan
- 5School of Life Sciences, University of Science and Technology of China, Hefei, China
- 6Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium
- 7VIB Center for Plant Systems Biology, Ghent, Belgium
- ↵*Corresponding author. Tel: +86 531 88362351; E‐mail: dingzhaojun{at}sdu.edu.cn
↵† These authors contributed equally to this work
Auxin and cytokinin synergistically mediate aluminum‐induced root growth inhibition in Arabidopsis, which is in contrast to the antagonistic action of both hormones in root meristem maintenance in unstressed conditions.
Synopsis
Auxin and cytokinin synergistically mediate aluminum‐induced root growth inhibition in Arabidopsis, which is in contrast to the antagonistic action of both hormones in root meristem maintenance in unstressed conditions.
Aluminium (Al) stress induces a local cytokinin response in the root‐apex transition zone.
IPTs are up‐regulated specifically in the root‐apex transition zone and promote cytokinin biosynthesis under Al stress.
Al‐induced cytokinin response is mediated by auxin, which acts downstream of ethylene signaling.
EMBO Reports (2017) 18: 1213–1230
- Received December 13, 2016.
- Revision received April 27, 2017.
- Accepted May 2, 2017.
- © 2017 The Authors
- Transposon‐driven transcription is a conserved feature of vertebrate spermatogenesis and transcript evolution
- Matthew P Davis1,†,
- Claudia Carrieri2,3,†,
- Harpreet K Saini1,
- Stijn van Dongen1,
- Tommaso Leonardi1,
- Giovanni Bussotti1,4,
- Jack M Monahan1,
- Tania Auchynnikava5,
- Angelo Bitetti6,
- Juri Rappsilber5,7,
- Robin C Allshire5,
- Alena Shkumatava6,
- Dónal O'Carroll (donal.ocarroll{at}ed.ac.uk)*,2,3 and
- Anton J Enright (aje{at}ebi.ac.uk)*,1
- 1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL‐EBI), Cambridge, UK
- 2European Molecular Biology Laboratory, Mouse Biology Outstation, Monterotondo, Italy
- 3MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
- 4Institut Pasteur – Bioinformatics and Biostatistics Hub, C3BI, USR 3756 IP CNRS, Paris, France
- 5Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
- 6Institut Curie – CNRS UMR3215, INSERM U934, Paris, France
- 7Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany
- ↵*
Corresponding author. Tel: +44 131 6519631; E‐mail: donal.ocarroll{at}ed.ac.uk
Corresponding author. Tel: +44 1223 492668; E‐mail: aje{at}ebi.ac.uk
↵† These authors contributed equally to the work
Large‐scale transcriptome analyses of the mouse germline shows that a significant fraction of noncoding transcripts are expressed in late spermatogenesis and are associated with endogenous retroviral elements that drive their transcription.
Synopsis
Large‐scale transcriptome analyses of the mouse germline shows that a significant fraction of noncoding transcripts are expressed in late spermatogenesis and are associated with endogenous retroviral elements that drive their transcription.
Transcriptome analyses of both noncoding and coding transcripts reveal a significant increase in gene expression during late stages of spermatogenesis.
Noncoding transcription in particular is increased and is associated with endogenous retroviral elements (ERVs) that overlay the transcriptional start sites of associated genes and drive their expression.
This germline repeat‐driven transcription is observed in other species. Some of these ERV‐driven loci appear to produce peptides even though they have computationally been determined to be non‐coding.
The testis is a hotspot for this phenomenon, however this effect is also observed in other tissues based on publicly available data.
EMBO Reports (2017) 18: 1231–1247
- Received February 10, 2017.
- Revision received March 29, 2017.
- Accepted April 11, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
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.
- The RNA helicase DHX9 establishes nucleolar heterochromatin, and this activity is required for embryonic stem cell differentiation
- Sergio Leone1,2,
- Dominik Bär1,
- Coenraad Frederik Slabber1,
- Damian Dalcher1,2 and
- Raffaella Santoro (raffaella.santoro{at}dmmd.uzh.ch)*,1
- 1Department of Molecular Mechanisms of Disease, University of Zurich, Zurich, Switzerland
- 2Molecular Life Science Program, Life Science Zurich Graduate School, University of Zurich, Zurich, Switzerland
- ↵*Corresponding author. Tel: +41 44 63 55475; E‐mail: raffaella.santoro{at}dmmd.uzh.ch
This study shows that DHX9 processes the lncRNA IGS‐rRNA into pRNA. This activity mediates nucleolar heterochromatic formation, which is required for ESCs to exit pluripotency.
Synopsis
This study shows that DHX9 processes the lncRNA IGS‐rRNA into pRNA. This activity mediates nucleolar heterochromatic formation, which is required for ESCs to exit pluripotency.
Processing of the lncRNA IGS‐rRNA into mature pRNA is mediated by DHX9.
DHX9‐mediated production of pRNA is required for recruitment of the repressor TIP5 to rRNA genes and establishment of nucleolar heterochromatin.
The activity of DHX9 to produce mature pRNA is required for ESC differentiation.
Formation of heterochromatin in the nucleolus via pRNA‐mediated recruitment of TIP5 to rRNA genes is required for ESC differentiation.
EMBO Reports (2017) 18: 1248–1262
- Received April 5, 2017.
- Revision received April 22, 2017.
- Accepted April 25, 2017.
- © 2017 The Authors
