TY - JOUR
T1 - Alternative glycosylation controls endoplasmic reticulum dynamics and tubular extension in mammalian cells
AU - Kerselidou, Despoina
AU - Dohai, Bushra Saeed
AU - Nelson, David R.
AU - Daakour, Sarah
AU - de Cock, Nicolas
AU - Oula Hassoun, Zahra Al
AU - Kim, Dae Kyum
AU - Olivet, Julien
AU - El Assal, Diana C.
AU - Jaiswal, Ashish
AU - Alzahmi, Amnah
AU - Saha, Deeya
AU - Pain, Charlotte
AU - Matthijssens, Filip
AU - Lemaitre, Pierre
AU - Herfs, Michael
AU - Chapuis, Julien
AU - Ghesquiere, Bart
AU - Vertommen, Didier
AU - Kriechbaumer, Verena
AU - Knoops, Kèvin
AU - Lopez-Iglesias, Carmen
AU - van Zandvoort, Marc
AU - Lambert, Jean Charles
AU - Hanson, Julien
AU - Desmet, Christophe
AU - Thiry, Marc
AU - Lauersen, Kyle J.
AU - Vidal, Marc
AU - van Vlierberghe, Pieter
AU - Dequiedt, Franck
AU - Salehi-Ashtiani, Kourosh
AU - Twizere, Jean Claude
N1 - Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
PY - 2021/5
Y1 - 2021/5
N2 - The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of guanosine triphosphate nucleotides. Among posttranslational 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 ER morphology and dynamics. We have integrated multiomics and superresolution 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. Last, our data illuminate the physical and functional aspects of the ER proteome-glycome-lipidome structure axis, with implications in biotechnology and medicine.
AB - The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of guanosine triphosphate nucleotides. Among posttranslational 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 ER morphology and dynamics. We have integrated multiomics and superresolution 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. Last, our data illuminate the physical and functional aspects of the ER proteome-glycome-lipidome structure axis, with implications in biotechnology and medicine.
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U2 - 10.1126/sciadv.abe8349
DO - 10.1126/sciadv.abe8349
M3 - Article
C2 - 33962942
AN - SCOPUS:85105687714
SN - 2375-2548
VL - 7
JO - Science Advances
JF - Science Advances
IS - 19
M1 - eabe8349
ER -