Exostosin-1 Glycosyltransferase Regulates Endoplasmic Reticulum Architecture and Dynamics
Type
PreprintAuthors
Kerselidou, DespoinaDohai, Bushra Saeed
Nelson, David R
Daakour, Sarah
De Cock, Nicolas
Kim, Dae-Kyum
Olivet, Julien
El Assal, Diana C
Jaiswal, Ashish
Saha, Deeya
Pain, Charlotte
Matthijssens, Filip
Lemaitre, Pierre
Herfs, Michael
Chapuis, Julien
Ghesquiere, Bart
Vertommen, Didier
Kriechbaumer, Verena
Knoops, Kevin
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
Date
2020-09-03Permanent link to this record
http://hdl.handle.net/10754/665119
Metadata
Show full item recordAbstract
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 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 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.Citation
Kerselidou, D., Dohai, B. S., Nelson, D. R., Daakour, S., De Cock, N., Kim, D.-K., … Twizere, J.-C. (2020). Exostosin-1 Glycosyltransferase Regulates Endoplasmic Reticulum Architecture and Dynamics. doi:10.1101/2020.09.02.275925Publisher
Cold Spring Harbor LaboratoryAdditional Links
http://biorxiv.org/lookup/doi/10.1101/2020.09.02.275925ae974a485f413a2113503eed53cd6c53
10.1101/2020.09.02.275925