Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade
- Ecole Polytechnique Fédérale de Lausanne, Switzerland
- Ecole Polytechnique Fédérale de Lausanne, Tajikistan
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
Vassily Hatzimanikatis
F Gisou van der Goot
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
- Philippe IH Bastiaens, Max Planck Institute of Molecular Physiology, Germany
Version history
- Received: April 15, 2017
- Accepted: August 7, 2017
- Accepted Manuscript published: August 15, 2017 (version 1)
- 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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Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade
eLife 6:e27826.
https://doi.org/10.7554/eLife.27826
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