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  • How stem cells get “turned on”
    1. Amy J Wagers (amy_wagers{at}harvard.edu) 1
    1. 1Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Stem Cell Institute, Cambridge, MA, USA

    Recent research began to link autophagic processes to the functional integrity of certain stem cells. A novel study published in this issue of The EMBO Journal reports on autophagic flux as crucial checkpoint to meet the energy demands during muscle stem cell activation.

    See also: AH Tang & TA Rando

    Activation of muscle stem cells requires defined energy levels. Recent results determine autophagic flux as crucial contributor to the metabolic state of muscle stem cells.

    Amy J Wagers
  • Transparent, Reproducible Data
    1. Bernd Pulverer (Bernd.Pulverer{at}embojournal.org) 1
    1. 1EMBO, Heidelberg, Germany

    New guidelines for the reporting of research and source data enhance the interpretation and reproducibility of published research.

    New guidelines for the reporting of research and source data enhance the interpretation and reproducibility of published research.

    Bernd Pulverer
  • Small, smaller… dendritic spine
    1. Pietro Pilo Boyl1 and
    2. Walter Witke (w.witke{at}uni-bonn.de) 1
    1. 1Institute of Genetics, University of Bonn, Bonn, Germany

    Spines are highly motile protrusions emerging from the dendritic shafts of neurons. The dynamics of these post‐synaptic structures are ruled by actin filament turnover. However, our understanding of the mechanisms of actin polymerization in dendritic spines is quite ambiguous. A recent study by the Giannone laboratory (Chazeau et al, 2014) is now shedding some light on the peculiar features of actin polymerization in dendritic spines, which are distinct from the known canonical mechanisms.

    See also: A Chazeau et al

    Super‐resolution microscopy describes actin dynamics and the spatial distribution of its regulators in dendritic spines, and reveals an organization different from traditional mechanisms of cortical actin control.

    Pietro Pilo Boyl, Walter Witke
  • The exosome‐binding factors Rrp6 and Rrp47 form a composite surface for recruiting the Mtr4 helicase
    1. Benjamin Schuch1,
    2. Monika Feigenbutz2,
    3. Debora L Makino1,
    4. Sebastian Falk1,
    5. Claire Basquin1,
    6. Phil Mitchell*,2 and
    7. Elena Conti*,1
    1. 1Structural Cell Biology Department, Max Planck Institute of Biochemistry, Martinsried, Germany
    2. 2Molecular Biology and Biotechnology Department, The University of Sheffield, Sheffield, UK
    1. * Corresponding author. Tel: +44 0114 222 2821; Fax: +44 0114 222 2787; E‐mail: p.j.mitchell{at}sheffield.ac.uk

      Corresponding author. Tel: +49 89 8578 3602; Fax: +49 89 8578 3605; E‐mail: conti{at}biochem.mpg.de

    Mtr4 is an RNA helicase involved in targeting nuclear RNAs for degradation. A new crystal structure reveals the basis for Mtr4 recruitment on the nuclear exosome through a direct interaction with Rrp6 and Rrp47.

    Synopsis

    Mtr4 is an RNA helicase involved in targeting nuclear RNAs for degradation. A new crystal structure reveals the basis for Mtr4 recruitment on the nuclear exosome through a direct interaction with Rrp6 and Rrp47.

    • The N‐terminal domains of S. cerevisiae Rrp6 and Rrp47 form a highly intertwined structural unit.

    • The Rrp6–Rrp47 complex creates a composite and conserved surface groove that binds the N‐terminus of Mtr4 and recruits Mtr4 to the nuclear exosome.

    • Structure‐based mutations of conserved residues within Rrp6 and Mtr4 disrupt their interaction, result in 5.8S RNA processing defects in vivo and inhibit growth of strains expressing a C‐terminal GFP fusion of Mtr4.

    • nuclear exosome
    • RNA degradation
    • X‐ray crystallography
    • yeast genetics
    • Received April 17, 2014.
    • Revision received August 8, 2014.
    • Accepted August 26, 2014.
    Benjamin Schuch, Monika Feigenbutz, Debora L Makino, Sebastian Falk, Claire Basquin, Phil Mitchell, Elena Conti
  • Peripheral natural killer cell maturation depends on the transcription factor Aiolos
    1. Melissa L Holmes1,,
    2. Nicholas D Huntington1,2,,
    3. Rebecca PL Thong1,,
    4. Jason Brady3,
    5. Yoshihiro Hayakawa4,
    6. Christopher E Andoniou5,6,
    7. Peter Fleming5,6,
    8. Wei Shi1,7,
    9. Gordon K Smyth1,8,
    10. Mariapia A Degli‐Esposti5,6,
    11. Gabrielle T Belz1,2,
    12. Axel Kallies1,2,
    13. Sebastian Carotta1,2,
    14. Mark J Smyth9,10 and
    15. Stephen L Nutt*,1,2
    1. 1The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia
    2. 2Department of Medical Biology, The University of Melbourne, Parkville, Vic., Australia
    3. 3Cancer Immunology Program, The Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia
    4. 4Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan
    5. 5Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Nedlands, WA, Australia
    6. 6Centre for Experimental Immunology, Lions Eye Institute, Nedlands, WA, Australia
    7. 7Department of Computing and Information Systems, University of Melbourne, Parkville, Vic., Australia
    8. 8The Department of Mathematics and Statistics, University of Melbourne, Parkville, Vic., Australia
    9. 9QIMR Berghofer Medical Research Institute, Herston, Qld, Australia
    10. 10School of Medicine, University of Queensland, Herston, Qld, Australia
    1. *Corresponding author. Tel: +61 3 9345 2483; Fax: +61 3 9347 0852; E‐mail: nutt{at}wehi.edu.au
    1. These authors contributed equally to this study

    Aiolos, a member of the Ikaros family of transcription factors, regulates the differentiation of mouse natural killer cells.

    Synopsis

    Aiolos, a member of the Ikaros family of transcription factors, regulates the differentiation of mouse natural killer (NK) cells.

    • NK cells constitutively express Aiolos.

    • Aiolos is required for final stage of NK‐cell development in the spleen.

    • Aiolos acts independently of the known regulators of NK‐cell maturation.

    • Despite their impaired maturation, NK cells lacking Aiolos show enhanced ability to control tumors.

    • differentiation
    • Ikzf3
    • NK cell
    • transcription
    • Received January 14, 2014.
    • Revision received September 1, 2014.
    • Accepted September 15, 2014.
    Melissa L Holmes, Nicholas D Huntington, Rebecca PL Thong, Jason Brady, Yoshihiro Hayakawa, Christopher E Andoniou, Peter Fleming, Wei Shi, Gordon K Smyth, Mariapia A Degli‐Esposti, Gabrielle T Belz, Axel Kallies, Sebastian Carotta, Mark J Smyth, Stephen L Nutt
  • Malt1 protease inactivation efficiently dampens immune responses but causes spontaneous autoimmunity
    1. Maike Jaworski1,
    2. Ben J Marsland2,
    3. Jasmine Gehrig3,
    4. Werner Held3,
    5. Stéphanie Favre1,
    6. Sanjiv A Luther1,
    7. Mai Perroud1,
    8. Déla Golshayan4,
    9. Olivier Gaide5 and
    10. Margot Thome*,1
    1. 1Department of Biochemistry, Center of Immunity and Infection, University of Lausanne, Epalinges, Switzerland
    2. 2Centre Hospitalier Universitaire Vaudois, Service de Pneumologie, Lausanne, Switzerland
    3. 3Department of Oncology, Ludwig Center for Cancer Research, University of Lausanne, Epalinges, Switzerland
    4. 4Centre Hospitalier Universitaire Vaudois, Transplantation Centre, Lausanne, Switzerland
    5. 5Centre Hospitalier Universitaire Vaudois, Service de Dermatologie et Vénéréologie, Lausanne, Switzerland
    1. *Corresponding author. Tel: +41 21 692 57 37; Fax: +41 21 692 57 05; E‐mail: margot.thomemiazza{at}unil.ch

    The protease activity of MALT1 is essential for the adaptive immune response, the generation of Treg cells, and the prevention of autoimmune gastritis.

    Synopsis

    The protease activity of MALT1 is essential for the adaptive immune response, but also for the generation of Treg cells and the prevention of autoimmune gastritis.

    • Mice expressing a catalytically inactive form of Malt1 (Malt1 knock‐in mice) are strongly immunodeficient and have impaired development of marginal zone B cells and B1 B cells.

    • Malt1 protease activity is required for efficient activation of lymphocytes, NK cells, and dendritic cells by immunoreceptors with ITAM motifs.

    • The absence of Malt1 protease activity protects mice against experimental autoimmune encephalitis and T‐cell transfer‐induced colitis.

    • The protease activity of Malt1 is also essential for the development of natural regulatory T cells (Tregs).

    • Malt1 knock‐in mice but not Malt1‐deficient mice develop autoimmune gastritis, most likely as a consequence of Malt1 scaffold‐driven immune responses in the absence of efficient Treg functions.

    • colitis
    • EAE
    • gastritis
    • NF‐κB
    • paracaspase
    • Received May 15, 2014.
    • Revision received September 17, 2014.
    • Accepted September 17, 2014.
    Maike Jaworski, Ben J Marsland, Jasmine Gehrig, Werner Held, Stéphanie Favre, Sanjiv A Luther, Mai Perroud, Déla Golshayan, Olivier Gaide, Margot Thome
  • Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation
    1. Ann H Tang1,2 and
    2. Thomas A Rando*,1,2,3,
    1. 1Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA
    2. 2Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA
    3. 3Neurology Service and Rehabilitation Research and Developmental Center of Excellence, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
    1. *Corresponding author. Tel: +1 650 849 1999; E‐mail: rando{at}stanford.edu
    1. This article has been contributed to by US Government employees and their work is in the public domain in the USA

    Tang and Rando report induction of autophagy by the nutrient sensor SIRT1 as crucial energy provider for efficient proliferation/differentiation in quiescent muscle satellite cells in vivo.

    Synopsis

    Tang and Rando report induction of autophagy by the nutrient sensor SIRT1 as crucial energy provider for efficient proliferation/differentiation in quiescent muscle satellite cells in vivo.

    • Muscle stem cells require autophagy to surmount a bioenergetic hurdle to break quiescence to enter an activated state.

    • Bioenergetic demands accompanying muscle stem cell activation induces autophagic flux.

    • These bioenergetic demands are signaled through SIRT1 to activate autophagy by interaction with ATG7 and through the AMPK pathway.

    • activation
    • autophagy
    • quiescence
    • satellite cell
    • SIRT1
    • Received February 19, 2014.
    • Revision received August 29, 2014.
    • Accepted September 1, 2014.
    Ann H Tang, Thomas A Rando