GIGA 2021 Annual Report 29 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, published 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 cells. 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 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 inmedicine, with the understanding of various diseases such as numerous cancers and Alzheimer’s diseases in which ER dynamics are affected. Reprogramming of N-glycosylation in the ER could also impact the production of recombinant proteins, therapeutic viral vectors and vaccines in mammalian cells.
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