Glycoproteome remodeling and organelle-specific N-glycosylation accompany neutrophil granulopoiesis

Rebeca Kawahara, Julian Ugonotti, Sayantani Chatterjee, Harry C. Tjondro, Ian Loke, Benjamin L. Parker, Vignesh Venkatakrishnan, Regis Dieckmann, Zeynep Sumer-Bayraktar, Anna Karlsson-Bengtsson, Johan Bylund, Morten Thaysen-Andersen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
12 Downloads (Pure)

Abstract

Neutrophils store microbicidal glycoproteins in cytosolic granules to fight intruding pathogens, but their granule distribution and formation mechanism(s) during granulopoiesis remain unmapped. Herein, we comprehensively profile the neutrophil N-glycoproteome with spatiotemporal resolution by analyzing four key types of intracellular organelles isolated from blood-derived neutrophils and during their maturation from bone marrow–derived progenitors using a glycomics-guided glycoproteomics approach. Interestingly, the organelles of resting neutrophils exhibited distinctive glycophenotypes including, most strikingly, highly truncated N-glycans low in α2,6-sialylation and Lewis fucosylation decorating a diverse set of microbicidal proteins (e.g., myeloperoxidase, azurocidin, neutrophil elastase) in the azurophilic granules. Excitingly, proteomics and transcriptomics data from discrete myeloid progenitor stages revealed that profound glycoproteome remodeling underpins the promyelocytic-to-metamyelocyte transition and that the glycophenotypic differences are driven primarily by dynamic changes in protein expression and less by changes within the glycosylation machinery. Notable exceptions were the oligosaccharyltransferase subunits responsible for initiation of N-glycoprotein biosynthesis that were strongly expressed in early myeloid progenitors correlating with relatively high levels of glycosylation of the microbicidal proteins in the azurophilic granules. Our study provides spatiotemporal insights into the complex neutrophil N-glycoproteome featuring intriguing organelle-specific N-glycosylation patterns formed by dynamic glycoproteome remodeling during the early maturation stages of the myeloid progenitors.

Original languageEnglish
Article numbere2303867120
Pages (from-to)1-11
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number36
DOIs
Publication statusPublished - 28 Aug 2023

Bibliographical note

Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • glycoproteome
  • granule
  • granulopoiesis
  • neutrophil
  • remodeling

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