What is it about?

Neutrophils are critical first-line responders to infection forming a potent line of innate immune defense. Neutrophils are armed with highly glycosylated microbicidal proteins essential for combatting invading pathogens, yet little is known about how, when, and where the microbicidal proteins are glycosylated during neutrophil maturation. Using systems glycobiology to investigate blood neutrophils and their progenitors, we find that profound glycoproteome remodeling accompanies the early neutrophil maturation phase when microbicidal glycoproteins are produced. The study provides spatiotemporal insights into the glycophenotype of key neutrophil compartments and the peculiar glycosylation that decorates microbicidal proteins.

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Why is it important?

The study forms a resource to guide future explorations targeting the biological roles and dysregulation of glycosylation in neutrophil-related disorders.

Perspectives

Our study is, to the best of our knowledge, the first system-wide report of granule- and progenitor-specific glycosylation in developing myeloid cells. In fact, organelle- and maturation stage-specific glycosylation appear scarcely investigated with recently available and highly informative glycoproteomics approaches. Our study therefore serves to illustrate how new technologies in systems glycobiology can be leveraged to generate valuable insight in a complex and dynamic biological system demonstrating specifically that protein glycosylation adds considerable structural and functional diversity to neutrophils with likely biological implications in innate immune processes and pathogen infection.

Morten Thaysen-Andersen
Macquarie University

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This page is a summary of: Glycoproteome remodeling and organelle-specific N -glycosylation accompany neutrophil granulopoiesis, Proceedings of the National Academy of Sciences, August 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2303867120.
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