Dynamics of CLIMP-63 S-acylation control ER morphology

Patrick A. Sandoz, Robin A. Denhardt-Eriksson, Laurence Abrami, Luciano A. Abriata, Gard Spreemann, Catherine Maclachlan, Sylvia Ho, Béatrice Kunz, Kathryn Hess, Graham Knott, Francisco S. Mesquita (), Vassily Hatzimanikatis () and F. Gisou Goot ()
Additional contact information
Patrick A. Sandoz: Global Health Institute, School of Life Sciences, EPFL
Robin A. Denhardt-Eriksson: Laboratory of Computational Systems Biotechnology, EPFL
Laurence Abrami: Global Health Institute, School of Life Sciences, EPFL
Luciano A. Abriata: Institute of Bioengineering, EPFL and Swiss Institute of Bioinformatics
Gard Spreemann: Brain Mind Institute, EPFL
Catherine Maclachlan: EPFL
Sylvia Ho: Global Health Institute, School of Life Sciences, EPFL
Béatrice Kunz: Global Health Institute, School of Life Sciences, EPFL
Kathryn Hess: Brain Mind Institute, EPFL
Graham Knott: EPFL
Francisco S. Mesquita: Global Health Institute, School of Life Sciences, EPFL
Vassily Hatzimanikatis: Laboratory of Computational Systems Biotechnology, EPFL
F. Gisou Goot: Global Health Institute, School of Life Sciences, EPFL

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract The complex architecture of the endoplasmic reticulum (ER) comprises distinct dynamic features, many at the nanoscale, that enable the coexistence of the nuclear envelope, regions of dense sheets and a branched tubular network that spans the cytoplasm. A key player in the formation of ER sheets is cytoskeleton-linking membrane protein 63 (CLIMP-63). The mechanisms by which CLIMP-63 coordinates ER structure remain elusive. Here, we address the impact of S-acylation, a reversible post-translational lipid modification, on CLIMP-63 cellular distribution and function. Combining native mass-spectrometry, with kinetic analysis of acylation and deacylation, and data-driven mathematical modelling, we obtain in-depth understanding of the CLIMP-63 life cycle. In the ER, it assembles into trimeric units. These occasionally exit the ER to reach the plasma membrane. However, the majority undergoes S-acylation by ZDHHC6 in the ER where they further assemble into highly stable super-complexes. Using super-resolution microscopy and focused ion beam electron microscopy, we show that CLIMP-63 acylation-deacylation controls the abundance and fenestration of ER sheets. Overall, this study uncovers a dynamic lipid post-translational regulation of ER architecture.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-35921-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35921-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-35921-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().