Alternative glycosylation controls endoplasmic reticulum dynamics and tubular extension in mammalian cells
Dohai, Bushra Saeed
Nelson, David R.
De Cock, Nicolas
Hassoun, Zahra Al Oula
El Assal, Diana C.
van Zandvoort, Marc
Lauersen, Kyle J.
Van Vlierberghe, Pieter
KAUST DepartmentBiological and Environmental Science and Engineering (BESE) Division
Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
Online Publication Date2021-05-07
Print Publication Date2021-05
Permanent link to this recordhttp://hdl.handle.net/10754/669164
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AbstractThe 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.
CitationKerselidou, D., Dohai, B. S., Nelson, D. R., Daakour, S., De Cock, N., Hassoun, Z. A. O., … Twizere, J.-C. (2021). Alternative glycosylation controls endoplasmic reticulum dynamics and tubular extension in mammalian cells. Science Advances, 7(19), eabe8349. doi:10.1126/sciadv.abe8349
SponsorsD.-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.
Except where otherwise noted, this item's license is described as 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).
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