Mammalian brain glycoproteins exhibit diminished glycan complexity compared to other tissues

Glycosylation is essential to brain development and function, but prior studies have often been limited to a single analytical technique and excluded region- and sex-specific analyses. Here, using several methodologies, we analyze Asn-linked and Ser/Thr/Tyr-linked protein glycosylation between brain regions and sexes in mice. Brain N-glycans are less complex in sequence and variety compared to other tissues, consisting predominantly of high-mannose and fucosylated/bisected structures. Most brain O-glycans are unbranched, sialylated O-GalNAc and O-mannose structures. A consistent pattern is observed between regions, and sex differences are minimal compared to those in plasma. Brain glycans correlate with RNA expression of their synthetic enzymes, and analysis of glycosylation genes in humans show a global downregulation in the brain compared to other tissues. We hypothesize that this restricted repertoire of protein glycans arises from their tight regulation in the brain. These results provide a roadmap for future studies of glycosylation in neurodevelopment and disease. Protein glycosylation is critical in brain development and disease. Here, the authors characterize brain glycans in detail, showing that they are simpler and more homogenous than glycans from other tissues and providing a basis for future studies of brain glycosylation.

Automated summary

In this study, the authors analyzed protein glycosylation in the brain of mice using multiple methodologies. They found that brain glycans are simpler and more homogenous than glycans from other tissues, and suggested that their restricted repertoire arises from tight regulation. These results provide a basis for future studies of glycosylation in neurodevelopment and disease.