Glycoproteome remodeling and organelle-specific N-glycosylation accompany neutrophil granulopoiesis
Journal article, 2023

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.







Rebeca Kawahara

Macquarie University

Nagoya University

Julian Ugonotti

Macquarie University

Sayantani Chatterjee

Macquarie University

Harry C. Tjondro

Macquarie University

Ian Loke

Cordlife Group

Benjamin L. Parker

University of Melbourne

Vignesh Venkatakrishnan

Chalmers, Life Sciences, Chemical Biology

University of Gothenburg

Régis Dieckmann

University of Gothenburg

Zeynep Sumer-Bayraktar

Macquarie University

Anna Karlsson-Bengtsson

Chalmers, Life Sciences

University of Gothenburg

Johan Bylund

University of Gothenburg

Morten Thaysen-Andersen

Macquarie University

Nagoya University

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 120 36 e2303867120

The glycome of emergency neutrophils and implications in sepsis

Swedish Research Council (VR) (2018-03077), 2019-01-01 -- 2024-12-31.

Subject Categories

Biochemistry and Molecular Biology




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