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  • 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
  • Inhibitor‐3 ensures bipolar mitotic spindle attachment by limiting association of SDS22 with kinetochore‐bound protein phosphatase‐1
    1. Annika Eiteneuer1,,
    2. Jonas Seiler1,,
    3. Matthias Weith1,
    4. Monique Beullens2,
    5. Bart Lesage2,
    6. Veronica Krenn3,
    7. Andrea Musacchio1,3,
    8. Mathieu Bollen2 and
    9. Hemmo Meyer*,1
    1. 1Centre for Medical Biotechnology, Faculty of Biology, University of Duisburg‐Essen, Essen, Germany
    2. 2Laboratory of Biosignaling & Therapeutics, KU Leuven, Department of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium
    3. 3Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    1. *Corresponding author. Tel: +49 201 183 4217; Fax: +49 201 183 4257; E‐mail: hemmo.meyer{at}uni-due.de
    1. These authors contributed equally to this work

    Intricate interplay of two PP1‐interacting regulators controls Aurora B‐mediated kinetochore phosphorylation to ensure proper chromosome segregation.

    Synopsis

    Reversible protein phosphorylation at kinetochores is essential for ensuring correct spindle attachment and chromosome segregation. Antagonism of Aurora B kinase action by protein phosphatase‐1 is controlled by intricate interplay of two PP1‐interacting regulators.

    • SDS22 is essential to activate KNL1‐bound PP1 at the kinetochore so that it can antagonize Aurora B during mitotic chromosome biorientation.

    • SDS22 itself does not normally localize to kinetochores and increased SDS22 binding to PP1 at the kinetochore in fact inhibits PP1 activity.

    • Inhibitor‐3 (I3) forms a complex with SDS22‐PP1 in solution and prevents association of SDS22 to KNL1‐bound PP1 to ensure PP1 activity at the kinetochore.

    • SDS22 in cooperation with I3 may act as a chaperone that activates PP1 in solution prior to recruitment to the kinetochore.

    • Aurora B
    • chromosome segregation
    • kinetochore
    • mitosis
    • protein phosphatase‐1
    • Received May 21, 2014.
    • Revision received September 8, 2014.
    • Accepted September 16, 2014.
    Annika Eiteneuer, Jonas Seiler, Matthias Weith, Monique Beullens, Bart Lesage, Veronica Krenn, Andrea Musacchio, Mathieu Bollen, Hemmo Meyer
  • OPA1‐dependent cristae modulation is essential for cellular adaptation to metabolic demand
    1. David A Patten1,
    2. Jacob Wong1,
    3. Mireille Khacho1,
    4. Vincent Soubannier2,
    5. Ryan J Mailloux3,
    6. Karine Pilon‐Larose1,
    7. Jason G MacLaurin1,
    8. David S Park1,
    9. Heidi M McBride2,
    10. Laura Trinkle‐Mulcahy1,
    11. Mary‐Ellen Harper3,
    12. Marc Germain*,4 and
    13. Ruth S Slack*,1
    1. 1Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, ON, Canada
    2. 2Montreal Neurological Institute, McGill University, Montreal, QC, Canada
    3. 3Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON, Canada
    4. 4Département de Biologie Médicale, Université du Québec à Trois‐Rivières, Trois‐Rivières, QC, Canada
    1. * Corresponding author. Tel: +1 613 562 5800; E‐mail: rslack{at}uottawa.ca

      Corresponding author. Tel: +1 819 376 5011 x3330; E‐mail: marc.germain1{at}uqtr.ca

    Metabolic stress causes inner mitochondrial membrane fusion protein OPA1 to interact with solute carriers and to oligomerize to regulate cristae shape, thereby maintaining mitochondrial activity under low energy availability.

    Synopsis

    Metabolic stress causes inner mitochondrial membrane fusion protein OPA1 to interact with solute carriers and to oligomerize to regulate cristae shape, thereby maintaining mitochondrial activity under low energy availability.

    • OPA1 dynamically responds to energy substrate availability, mediating changes in cristae ultrastructure.

    • OPA1‐mediated cristae changes are required for cell adaptation to metabolic demand, independently of OPA1 fusion activity.

    • SLC25A proteins interact with OPA1 and modulate its function.

    • OGC (SLC25A11) affects how OPA1 oligomerizes in response to starvation, mediating changes in mitochondrial function.

    • ATP synthase
    • cristae
    • mitochondria
    • OPA1
    • SLC25A
    • Received February 27, 2014.
    • Revision received August 28, 2014.
    • Accepted August 29, 2014.
    David A Patten, Jacob Wong, Mireille Khacho, Vincent Soubannier, Ryan J Mailloux, Karine Pilon‐Larose, Jason G MacLaurin, David S Park, Heidi M McBride, Laura Trinkle‐Mulcahy, Mary‐Ellen Harper, Marc Germain, Ruth S Slack