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

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

Research output: Contribution to journalArticlepeer-review

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Abstract

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.
Original languageEnglish (US)
Pages (from-to)eabe8349
JournalScience Advances
Volume7
Issue number19
DOIs
StatePublished - May 7 2021

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