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Alternative glycosylation controls endoplasmic reticulum dynamics and tubular extension in mammalian cells.

Despoina KerselidouBushra Saeed DohaiDavid Roy NelsonSarah DaakourNicolas De CockZahra Al Oula HassounDae-Kyum KimJulien OlivetDiana C El AssalAshish JaiswalAmnah AlzahmiDeeya SahaCharlotte PainFilip MatthijssensPierre LemaitreMichael HerfsJulien ChapuisBart GhesquiereDidier VertommenVerena KriechbaumerKèvin KnoopsCarmen Lopez-IglesiasMarc van ZandvoortJean-Charles LambertJulien HansonChristophe J DesmetMarc ThiryKyle J LauersenMarc VidalPieter Van VlierbergheFranck DequiedtKourosh Salehi-AshtianiJean-Claude Twizere
Published in: Science advances (2021)
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.
Keyphrases
  • endoplasmic reticulum
  • estrogen receptor
  • breast cancer cells
  • high resolution
  • signaling pathway
  • transcription factor
  • single cell
  • mesenchymal stem cells
  • cell therapy
  • high glucose
  • data analysis