Major advance in the understanding of the dynamics of intracellular membranes in an animal cell
The team of Jean-Claude Twizere (Laboratory of Viral Interactomes, GIGA-MBD), in collaboration with 5 other GIGA laboratories, as well as several other Belgian and international teams, publishes a study in Science Advances that may have a major impact in the understanding of the internal dynamics in an animal cell.
The Endoplasmic Reticulum (ER) is the largest organelle of eucaryotic cell. This organelle structurally organized into a vast membranous network, was first observed in the 1950s by Porter and Palade using electron microscopy. Constitutive proteins of the ER tubular network were identified recently, in 2010 (Shibata et al. Cell 143, 774-788) and 2017 (Powers et al. Nature 543, 257-260). However, as the ER adapts its architecture according to the cellular state, the control of this dynamic rearrangement remained unclear.
In this study, Despoina Kerselidou, PhD student in Jean-Claude Twizere’s lab, showed that exostosin-1 (EXT1) glycosyltransferase, an enzyme involved in the polymerization of glycans destined to the cellular membrane, is also a key regulator of ER morphology and dynamics.
Using genetic engineering techniques, electron and super-resolution microscopy, and a series of complex -omics analyses, these teams showed that knock-out or -down of EXT1 affects ER morphology and induces ER membrane network extension. These phenotypic changes originate from reprogramming of N-glycosylation reactions and significantly increase cellular metabolic activities.
This study could have implications both in medicine, with the understanding of various diseases such as numerous cancers and Alzheimer's diseases in which ER dynamics are affected, and also in the biotechnology, with the optimization animal cell productivity. Reprogramming of N-glycosylation in the ER could, in particular, impact the production of recombinant proteins, therapeutic viral vectors and vaccines in mammalian cells. As illustrated by the current Covid19 pandemic, large-scale adenoviral vaccines’ manufacturing is significantly impacted by mammalian cells limited productivity.
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 Kriechbaumer, Kèvin 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
Sci Adv. 2021 May 7;7(19):eabe8349. doi: 10.1126/sciadv.abe8349. Print 2021 May.