Journal Article


Alternative glycosylation controls endoplasmic reticulum dynamics and tubular extension in mammalian cells

Abstract

The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of GTP nucleotides. Among post-translational modifications initiated at the ER level, glycosylation is the most common reaction. However, our understanding of the impact of glycosylation on the ER structure remains unclear. Here, we show that Exostosin-1 (EXT1) glycosyltransferase, an enzyme involved in N-glycosylation, is a key regulator of the ER morphology and dynamics. We have integrated multi-omics data and super-resolution imaging to characterize the broad effect of EXT1 inactivation, including the ER shape-dynamics-function relationships in mammalian cells. We have observed that inactivating EXT1 induces cell enlargement and enhances metabolic switches such as protein secretion. In particular, suppressing EXT1 in mouse thymocytes causes developmental dysfunctions associated with the ER network extension. Finally, our data illuminate the physical and functional aspects of the ER proteome-glycome-lipidome-structure axis, with implications in biotechnology and medicine.

Attached files

Authors

Kerselidou, Despoina
Dohai, Bushra Saeed
Nelson, David R.
Daakour, Sarah
De Cock, Nicolas
Al Oula Hassoun, Zahra
Kim, Dae-Kyum
Olivet, Julien
El Assal, Diana C.
Jaiswal, Ashish
Alzahmi, Amnah
Saha, Deeya
Pain, Charlotte
Matthijssens, Filip
Lemaitre, Pierre
Herfs, Michael
Chapuis, Julien
Ghesquiere, Bart
Vertommen, Didier
Kriechbaumer, Verena
Knoops, Kèvin
Lopez-Iglesias, Carmen
van Zandvoort, Marc
Lambert, Jean-Charles
Hanson, Julien
Desmet, Christophe
Thiry, Marc
Lauersen, Kyle J.
Vidal, Marc
Van Vlierberghe, Pieter
Dequiedt, Franck
Salehi-Ashtiani, Kourosh
Twizere, Jean-Claude

Oxford Brookes departments

Department of Biological and Medical Sciences

Dates

Year of publication: 2021
Date of RADAR deposit: 2021-03-23


Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 International License


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