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  • A sulfur‐based transport pathway in Cu+‐ATPases
    <div xmlns="http://www.w3.org/1999/xhtml">A sulfur‐based transport pathway in Cu<sup>+</sup>‐ATPases</div>
    1. Daniel Mattle1,245,
    2. Limei Zhang26,
    3. Oleg Sitsel1,
    4. Lotte Thue Pedersen1,
    5. Maria Rosa Moncelli3,
    6. Francesco Tadini‐Buoninsegni3,
    7. Pontus Gourdon178,
    8. Douglas C Rees2,
    9. Poul Nissen1 and
    10. Gabriele Meloni*,1,2
    1. 1Centre for Membrane Pumps in Cells and Disease – PUMPkin, Department of Molecular Biology and Genetics, Danish National Research Foundation Aarhus University, Aarhus C, Denmark
    2. 2Division of Chemistry and Chemical Engineering and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA, USA
    3. 3Department of Chemistry ‘Ugo Schiff’, University of Florence, Sesto Fiorentino, Italy
    4. 4Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, Switzerland
    5. 5Roche Pharma Research and Early Development, Roche Innovation Center Basel Discovery Technologies, Basel, Switzerland
    6. 6Department of Biochemistry and Redox Biology Center, University of Nebraska‐Lincoln, Lincoln, NE, USA
    7. 7Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
    8. 8Department of Experimental Medical Science, Lund University, Lund, Sweden
    1. *Corresponding author. Tel: +1 6263952662; E‐mail: gmeloni{at}caltech.edu or gmeloni{at}mbg.au.dk

    This study identifies a copper transport pathway dominated by sulfur‐based residues for the Cu+‐ATPase LpCopA from Legionella pneumophila thus providing insights into how metal selectivity and transport is achieved in Cu+‐ATPases.

    Synopsis

    This study identifies a copper transport pathway dominated by sulfur‐based residues for the Cu+‐ATPase LpCopA from Legionella pneumophila thus providing insights into how metal selectivity and transport is achieved in Cu+‐ATPases.

    • Cu+ selection and subsequent extrusion involves a single high‐affinity transmembrane Cu+ binding site located at transmembrane helices (TM) 4 and 6.

    • The transmembrane translocation conduit is dominated by sulfur‐containing residues.

    • Conserved transmembrane polar residues in TM4‐6 possess distinct roles in the transport catalytic cycle.

    • charge transfer measurements
    • Cu+ coordination
    • Cu+‐ATPase
    • membrane protein transporter
    • P‐type ATPase
    • X‐ray absorption spectroscopy
    • Received November 26, 2014.
    • Revision received March 13, 2015.
    • Accepted March 31, 2015.
    Daniel Mattle, Limei Zhang, Oleg Sitsel, Lotte Thue Pedersen, Maria Rosa Moncelli, Francesco Tadini‐Buoninsegni, Pontus Gourdon, Douglas C Rees, Poul Nissen, Gabriele Meloni
  • Simulating the human brainScientists have started various major projects to simulate and understand the brain, but many neuroscientists remain sceptical about their scope and aims
    Simulating the human brain

    Scientists have started various major projects to simulate and understand the brain, but many neuroscientists remain sceptical about their scope and aims

    1. Philip Hunter, Freelance journalist (ph{at}philiphunter.com) 1
    1. 1 London, UK

    Several large‐scale projects have begun or are being planned to understand the human brain and find new therapeutic approaches to neurological diseases and disorders. Yet, many neurobiologists are concerned that some of the aims are too ambitious and risk wasting precious research funding.

    Philip Hunter
  • DCC functions as an accelerator of thalamocortical axonal growth downstream of spontaneous thalamic activity
    DCC functions as an accelerator of thalamocortical axonal growth downstream of spontaneous thalamic activity
    1. Mar Castillo‐Paterna1,
    2. Verónica Moreno‐Juan1,
    3. Anton Filipchuk1,
    4. Luis Rodríguez‐Malmierca1,
    5. Rafael Susín1 and
    6. Guillermina López‐Bendito*,1
    1. 1Instituto de Neurociencias de Alicante, Universidad Miguel Hernández‐Consejo Superior de Investigaciones Científicas (UMH‐CSIC), San Joan d'Alacant, Spain
    1. *Corresponding author. Tel: +34‐965‐919278; E‐mail: g.lbendito{at}umh.es

    This study identifies the Netrin‐1 receptor DCC as an accelerator for thalamic axon growth. Dcc transcription is regulated by spontaneous calcium activity in thalamocortical neurons, and an AP‐1‐binding site in the Dcc promoter that is crucial for the activity‐dependent regulation of this gene is described.

    Synopsis

    This study identifies the Netrin‐1 receptor DCC as an accelerator for thalamic axon growth. Dcc transcription is regulated by spontaneous calcium activity in thalamocortical neurons, and an AP‐1‐binding site in the Dcc promoter that is crucial for the activity‐dependent regulation of this gene is described.

    • Dcc operates downstream of spontaneous activity to control TCA growth.

    • Dcc functions as an accelerator for TCA growth.

    • An AP‐1 site in the Dcc promoter is essential for the activity‐dependent Dcc expression.

    • axon growth
    • development
    • Netrin‐1/Dcc signalling
    • spontaneous activity
    • thalamus
    • Received November 20, 2014.
    • Revision received April 12, 2015.
    • Accepted April 13, 2015.
    Mar Castillo‐Paterna, Verónica Moreno‐Juan, Anton Filipchuk, Luis Rodríguez‐Malmierca, Rafael Susín, Guillermina López‐Bendito
  • Insect proteins—a new source for animal feedThe use of insect larvae to recycle food waste in high‐quality protein for livestock and aquaculture feeds is held back largely owing to regulatory hurdles
    Insect proteins—a new source for animal feed

    The use of insect larvae to recycle food waste in high‐quality protein for livestock and aquaculture feeds is held back largely owing to regulatory hurdles

    1. Andreas Stamer (andreas.stamer{at}fibl.org) 1
    1. 1Department of Livestock Sciences in Frick, Research Institute of Organic Agriculture, Frick, Switzerland

    Insects could be an environmentally sustainable component of both livestock and human diets, especially as they can be fed on food waste. However, health regulations and Western dietary habits are holding back this promising new approach.

    Andreas Stamer
  • Keeping enzymes kosherSacred and secular biotech production
    Keeping enzymes kosher

    Sacred and secular biotech production

    1. Johan Fischer (johanf{at}ruc.dk) 1
    1. 1Roskilde University, Roskilde, Denmark

    Biotech companies increasingly seek certification for compliance with religious and dietary requirements in order to address new consumer markets. Technology plays a crucial role in such inspections alongside centuries old traditions and practices.

    Johan Fischer
  • Another face of RIPK1
    Another face of RIPK1
    1. Douglas R Green (douglas.green{at}stjude.org) 1
    1. 1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA

    Receptor‐interacting protein kinase‐1 (RIPK1) sits at a signaling node controlling a number of functional pathways. These include both positive and negative control of apoptosis and necroptosis (a form of regulated necrosis). In this issue of EMBO Reports, Yonekawa and colleagues describe another function for RIPK1, the inhibition of autophagy via ERK‐mediated phosphorylation of the transcription factor, TFEB [1]. Their findings are considered in the context of RIPK1 signaling, and how it is engaged.

    See also: T Yonekawa et al

    In this issue of EMBO Reports, RIPK1 is shown to inhibit basal autophagy, thereby regulating cellular sensitivity to apoptosis. This is discussed in the context of other RIPK1 functions related to cell death.

    Douglas R Green
  • Phosphorylation of the exchange factor DENND3 by ULK in response to starvation activates Rab12 and induces autophagy
    Phosphorylation of the exchange factor DENND3 by ULK in response to starvation activates Rab12 and induces autophagy
    1. Jie Xu*,1,
    2. Maryam Fotouhi1 and
    3. Peter S McPherson*,1
    1. 1Department of Neurology and Neurosurgery, Montreal Neurological Institute McGill University, Montreal, Quebec H3A 2B4, Canada
    1. * Corresponding author. Tel: +1 514 398 7355; E‐mail: peter.mcpherson{at}mcgill.ca

      Corresponding author. Tel: +1 514 398 6644 ext 00209; E‐mail: jie.xu3{at}mail.mcgill.ca

    The GEF DENND3 is shown to have a crucial role in autophagy, under the control of ULK‐mediated phosphoregulation. Phosphorylation upregulates DENND3 GEF activity towards Rab12, facilitating autophagosome trafficking.

    Synopsis

    The GEF DENND3 is shown to have a crucial role in autophagy, under the control of ULK‐mediated phosphoregulation. Phosphorylation upregulates DENND3 GEF activity towards Rab12, facilitating autophagosome trafficking.

    • This study reveals regulation of membrane trafficking downstream of a key signal transduction pathway, uncovering a new mechanism of ULK function in autophagy.

    • We provide the first evidence that ULK phosphorylation of a substrate creates a 14‐3‐3 docking site.

    • Rab12 binds LC3 and co‐localizes with autophagosomes, facilitating autophagosome trafficking

    • 14‐3‐3
    • LC3
    • DENN domain
    • GEF
    • guanine nucleotide exchange factor
    • Received December 15, 2014.
    • Revision received March 30, 2015.
    • Accepted March 31, 2015.
    Jie Xu, Maryam Fotouhi, Peter S McPherson