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- ArticleThe intramembrane protease SPPL2c promotes male germ cell development by cleaving phospholamban
- Johannes Niemeyer1,†,
- Torben Mentrup1,2,†,
- Ronny Heidasch3,†,
- Stephan A Müller4,5,
- Uddipta Biswas2,
- Rieke Meyer1,
- Alkmini A Papadopoulou6,
- Verena Dederer3,
- Martina Haug‐Kröper6,
- Vivian Adamski1,
- Renate Lüllmann‐Rauch7,
- Martin Bergmann8,
- Artur Mayerhofer9,
- Paul Saftig1,
- Gunther Wennemuth10,
- Rolf Jessberger2,
- Regina Fluhrer4,6,
- Stefan F Lichtenthaler4,5,11,
- Marius K Lemberg3 and
- Bernd Schröder (bernd.schroeder{at}tu-dresden.de)*,1,2
- 1Biochemical Institute, Christian‐Albrechts‐University of Kiel, Kiel, Germany
- 2Institute of Physiological Chemistry, Technische Universität Dresden, Dresden, Germany
- 3Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ‐ZMBH Allianz, Heidelberg, Germany
- 4DZNE – German Center for Neurodegenerative Diseases, Munich, Germany
- 5Neuroproteomics, School of Medicine, Klinikum rechts der Isar and Institute for Advanced Study, Technical University of Munich, Munich, Germany
- 6Institute for Metabolic Biochemistry, Biomedical Center (BMC) München, Ludwig Maximilians University of Munich, Munich, Germany
- 7Institute of Anatomy, Christian‐Albrechts‐University of Kiel, Kiel, Germany
- 8Institute of Veterinary Anatomy, Justus Liebig University of Gießen, Gießen, Germany
- 9Cell Biology, Anatomy III, Biomedical Center (BMC) München, Ludwig Maximilians University of Munich, Munich, Germany
- 10Institute of Anatomy, University Hospital, Duisburg‐Essen University, Essen, Germany
- 11Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
- ↵*Corresponding author. Tel: +49 351 458 6450; Fax: +49 351 458 6307; E‐mail: bernd.schroeder{at}tu-dresden.de
↵† These authors contributed equally to this work
The intramembrane protease SPPL2c is critical for the turnover of selected tail‐anchored proteins in spermatids and thereby supports differentiation and function of male germ cells.
Synopsis
The intramembrane protease SPPL2c is critical for the turnover of selected tail‐anchored proteins in spermatids and thereby supports differentiation and function of male germ cells.
The presenilin‐homologue Signal peptide peptidase‐like 2c is an ER‐resident intramembrane protease endogenously expressed in murine and human spermatids.
SPPL2c processes selected tail‐anchored proteins with a substrate spectrum distinct from that of Signal peptide peptidase (SPP).
SPPL2c‐deficient mice show a partial loss of elongated spermatids and reduced motility of mature spermatozoa.
Phospholamban represents a physiological SPPL2c substrate in murine testis.
EMBO Reports (2019) e46449
- Received May 18, 2018.
- Revision received December 21, 2018.
- Accepted December 21, 2018.
- © 2019 The Authors
- ArticleSignal Peptide Peptidase‐Like 2c (SPPL2c) impairs vesicular transport and cleavage of SNARE proteins
- Alkmini A Papadopoulou1,
- Stephan A Müller2,
- Torben Mentrup3,
- Merav D Shmueli2,4,5,
- Johannes Niemeyer3,
- Martina Haug‐Kröper1,
- Julia von Blume6,
- Artur Mayerhofer7,
- Regina Feederle2,8,9,
- Bernd Schröder3,10,
- Stefan F Lichtenthaler2,5,9 and
- Regina Fluhrer (regina.fluhrer{at}med.uni-muenchen.de)*,1,2
- 1Institute for Metabolic Biochemistry, Biomedical Center (BMC), Ludwig‐Maximilians University Munich, Munich, Germany
- 2DZNE – German Center for Neurodegenerative Diseases, Munich, Germany
- 3Biochemical Institute, Christian Albrechts University of Kiel, Kiel, Germany
- 4Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
- 5Neuroproteomics, School of Medicine, Klinikum Rechts der Isar, and Institute for Advanced Study, Technical University Munich, Munich, Germany
- 6Max Planck Institute of Biochemistry, Martinsried, Germany
- 7Cell Biology, Anatomy III, Biomedical Center (BMC), Ludwig‐Maximilians University Munich, Munich, Germany
- 8Institute for Diabetes and Obesity, Monoclonal Antibody Core Facility, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany
- 9Munich Center for Systems Neurology (SyNergy), Munich, Germany
- 10Institute for Physiological Chemistry, Technische Universität Dresden, Dresden, Germany
- ↵*Corresponding author. Tel: +49 89 4400 46505; E‐mail: regina.fluhrer{at}med.uni-muenchen.de
Signal peptide peptidase‐like 2c (SPPL2c), thus far considered an orphan protease, is catalytically active and expressed in maturating spermatids. SPPL2c cleaves SNARE proteins and impairs vesicular transport and Golgi integrity.
Synopsis
Signal peptide peptidase‐like 2c (SPPL2c), thus far considered an orphan protease, is catalytically active and expressed in maturating spermatids. SPPL2c cleaves SNARE proteins and impairs vesicular transport and Golgi integrity.
Proteomic analysis of HEK293 cells ectopically expressing SPPL2c reveals potential candidate substrates, among them various SNARE proteins.
SPPL2c is a catalytically active intramembrane aspartyl protease of the GxGD‐type.
SPPL2c supports acrosome formation in the maturating spermatids.
EMBO Reports (2019) e46451
- Received May 18, 2018.
- Revision received December 7, 2018.
- Accepted December 21, 2018.
- © 2019 The Authors
- CorrespondenceResponse by the author
- Melissa Suran, Journalist (mnsuran{at}u.northwestern.edu)1
The response by the author.
EMBO Reports (2019) e47720
- © 2019 The Author
- Science & SocietyFinding levers for culture change in science—the power of glocalLocal initiatives to change the culture of science from competition to collaboration and cooperation
Local initiatives to change the culture of science from competition to collaboration and cooperation
To tackle the great challenges of our time, the culture of science needs to change to a more collaborative one. Such change would start locally to spread out into the global scientific community.
EMBO Reports (2019)e46980
- © 2019 The Author
- Science & SocietyThe anti‐vaccination debate and the microbiomeHow paradigm shifts in the life sciences create new challenges for the vaccination debate
How paradigm shifts in the life sciences create new challenges for the vaccination debate
- Stephan Guttinger (s.m.guettinger{at}lse.ac.uk)1
Anti‐vaccine activists misuse findings from microbiome research to push their agenda. It requires a concerted response by the scientific community to confront the misinformation.
EMBO Reports (2019) e47709
- © 2019 The Author
- ArticleThe E3 ligase Highwire promotes synaptic transmission by targeting the NAD‐synthesizing enzyme dNmnat
- Alexandra Russo1,
- Pragya Goel2,
- EJ Brace1,
- Chris Buser3,
- Dion Dickman2 and
- Aaron DiAntonio (diantonio{at}wustl.edu)*,1
- 1Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
- 2Department of Neurobiology, University of Southern California, Los Angeles, CA, USA
- 3Oak Crest Institute of Science, Monrovia, CA, USA
- ↵*Corresponding author. Tel: +1 314 362 9925: E‐mail: diantonio{at}wustl.edu
The E3 ubiquitin ligase Highwire targets and downregulates the NAD+ synthesizing enzyme dNmnat to promote evoked synaptic transmission at the Drosophila larval neuromuscular junction.
Synopsis
The E3 ubiquitin ligase Highwire targets and downregulates the NAD+ synthesizing enzyme dNmnat to promote evoked synaptic transmission at the Drosophila larval neuromuscular junction.
Hiw mutants exhibit defects in evoked synaptic transmission, release probability, and active zone T‐bar structure, each of which are dNmnat‐dependent.
Excess dNmnat in a wildtype background can depress evoked release, and this is dependent on the catalytic activity of dNmnat, suggesting that excess NAD+ synthesis drives the defects in synaptic transmission.
Hiw balances the axoprotective and synapse‐inhibitory functions of dNmnat by tightly regulating dNmnat levels in Drosophila.
EMBO Reports (2019) e46975
- Received August 28, 2018.
- Revision received December 31, 2018.
- Accepted January 7, 2019.
- © 2019 The Authors
