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Exostosin-1 Glycosyltransferase Regulates Endoplasmic Reticulum Architecture and Dynamics

Authors :
Diana C. El Assal
Ashish Jaiswal
Nicolas De Cock
Pieter Van Vlierberghe
Jean-Charles Lambert
Filip Matthijssens
Julien Olivet
David R. Nelson
Despoina Kerselidou
Julien Hanson
Franck Dequiedt
Verena Kriechbaumer
Carmen López-Iglesias
Dae-Kyum Kim
Charlotte Pain
Marc Vidal
Julien Chapuis
Jean-Claude Twizere
Deeya Saha
Michael Herfs
Marc Thiry
Marc A. M. J. van Zandvoort
Pierre Lemaitre
Sarah Daakour
Kourosh Salehi-Ashtiani
Bart Ghesquière
Bushra Saeed Dohai
Kyle J. Lauersen
Christophe Desmet
Kèvin Knoops
Didier Vertommen
Publication Year :
2020
Publisher :
Cold Spring Harbor Laboratory, 2020.

Abstract

SUMMARYThe 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 ER structure remains unclear. Here, we show that Exostosin-1 (EXT1) glycosyltransferase, an enzyme involved inN-glycosylation, is a key regulator of ER morphology and dynamics. We have integrated multi-omics data and super-resolution imaging to characterize the broad effect of EXT1 inactivation, including 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 to ER network extension. Our findings suggest that EXT1 drives glycosylation reactions involving ER structural proteins and high-energy nucleotide sugars, which might also apply to other organelles.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........7f19b2b8194e876ecbc6edd74387432a
Full Text :
https://doi.org/10.1101/2020.09.02.275925