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 - Hassoun, Zahra Al Oula
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 - KAUST Repository Item: Exported on 2021-05-12
Acknowledgements: D.-K.K. was supported by Banting Postdoctoral Fellowship of Canada and Basic Science Research Program through the National Research
Foundation of Korea (NRF) funded by the Ministry of Education (2017R1A6A3A03004385). B.S.D., S.D., D.R.N., A.J., D.C.E.A., and K.S.-A. were supported by New York University Abu Dhabi (NYUAD) Institute grant 73 71210 CGSB9 and NYUAD Faculty Research Fund AD060. D.K. was
supported by an FRS-FNRS-Télévie Fellowship no. 7651317F (J.-C.T.). J.-C.T. is a Maitre de Recherche of the FRS-FNRS. Primarily, the Fonds de la Recherche Scientifique (FRS-FNRS) and the Fonds Leon Fredericq grants supported this work.
PY - 2021/5/7
Y1 - 2021/5/7
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.
UR - http://hdl.handle.net/10754/669164
UR - https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.abe8349
U2 - 10.1126/sciadv.abe8349
DO - 10.1126/sciadv.abe8349
M3 - Article
C2 - 33962942
SN - 2375-2548
VL - 7
SP - eabe8349
JO - Science advances
JF - Science advances
IS - 19
ER -