1. Cell Biology
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Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade

  1. Laurence Abrami
  2. Tiziano Dallavilla
  3. Patrick A Sandoz
  4. Mustafa Demir
  5. Béatrice Kunz
  6. Georgios Savoglidis
  7. Vassily Hatzimanikatis  Is a corresponding author
  8. F Gisou van der Goot  Is a corresponding author
  1. Ecole Polytechnique Fédérale de Lausanne, Switzerland
  2. Ecole Polytechnique Fédérale de Lausanne, Tajikistan
Research Article
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Cite this article as: eLife 2017;6:e27826 doi: 10.7554/eLife.27826

Abstract

S-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC family of palmitoyltransferases is very limited. Here we show that mammalian DHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, DHHC16, revealing the first palmitoylation cascade. Combination of site specific mutagenesis of the three DHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the 8 differentially palmitoylated DHHC6 species. We found that species rapidly interconvert through the action of DHHC16 and the Acyl Protein Thioesterase APT2, that each species varies in terms of turnover rate and activity, altogether allowing the cell to robustly tune its DHHC6 activity.

Article and author information

Author details

  1. Laurence Abrami

    Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Tiziano Dallavilla

    Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Patrick A Sandoz

    Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8379-7267
  4. Mustafa Demir

    Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Béatrice Kunz

    Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Georgios Savoglidis

    ISIC, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Tajikistan
    Competing interests
    The authors declare that no competing interests exist.
  7. Vassily Hatzimanikatis

    ISIC, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    For correspondence
    vassily.hatzimanikatis@epfl.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6432-4694
  8. F Gisou van der Goot

    Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    For correspondence
    gisou.vandergoot@epfl.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8522-274X

Funding

European Research Council (340260 PalmERa)

  • F Gisou van der Goot

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SystemsX iPhD Fellowship)

  • Tiziano Dallavilla

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SystemsX.ch LipidX RTD)

  • Vassily Hatzimanikatis
  • F Gisou van der Goot

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Division III Grant)

  • F Gisou van der Goot

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Philippe IH Bastiaens, Max Planck Institute of Molecular Physiology, Germany

Publication history

  1. Received: April 15, 2017
  2. Accepted: August 7, 2017
  3. Accepted Manuscript published: August 15, 2017 (version 1)
  4. Version of Record published: September 4, 2017 (version 2)

Copyright

© 2017, Abrami et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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