O- GalNAc glycans are enriched in neuronal tracts and regulate nodes of Ranvier

• 成果类型: Article
• 署名作者: Noel, Maxence; Suttapitugsakul, Suttipong; Cummings, Richard D.; Mealer, Robert G.
• 署名单位: Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11070
• DOI: 10.1073/pnas.2418949122
• 发表日期: 2025-02-28
• 关键词: myelin-associated glycoprotein; linked glycosylation; specificity; lectin; cells; gene; behab/brevican; purification; disease; cosmc

摘要

Protein O-glycosylation is a critical modification in the brain, as genetic variants in the pathway are associated with common and severe neuropsychiatric phenotypes. However, little is known about the most abundant O- glycans in the mammalian brain, which are N- acetylgalactosamine (O- GalNAc) linked. Here, we determined the spatial localization, protein carriers, and cellular function of O- GalNAc glycans in the mouse brain. We observed striking spatial enrichment of O- GalNAc glycans in neuronal tracts, and specifically at nodes of Ranvier, specialized structures involved in signal propagation in the brain. Glycoproteomic analysis revealed that more than half of the identified O- GalNAc glycans were present on chondroitin sulfate proteoglycans termed lecticans, and display both domain enrichment and regional heterogeneity. Inhibition of O- GalNAc synthesis in neurons reduced binding of Siglec-4, a known regulator of neurite growth, and shortened the length of nodes of Ranvier. This work establishes a function of O- GalNAc glycans in the brain and will inform future studies on their role in development and disease.