1. Alternative glycosylation controls endoplasmic reticulum dynamics and tubular extension in mammalian cells
- Author
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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, 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, and Twizere, Jean-Claude
- 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.
- Published
- 2021