Map of the Neuronal Tissue O-glycoproteome Reveal Specific Traits in the Secretogranin Family

Protein O-glycosylation is an abundant PTM of the central nervous system and impairments in O-glycosylation cause severe developmental disorders most with prominent neurological involvement. Despite recent advancements, lack of insight into targets of protein O-glycosylation in neuronal tissues severely hampers progression in unravelling disease etiology. Here we report a comprehensive map of GalNAc-type O-glycoproteins (>800) and O-glycosites (>4,000) from neuronal tissues and cell lines compiled in a web-based resource. We identified abundant O-glycosites within major classes of proteins involved in neuroplasticity such as perineural nets, synapse formation, axon guidance, membrane remodeling and dense core granulogenesis. We demonstrate that Chromogranin A, a key player in neurotransmitter signaling, has abundant O-GalNAc as well as glycosaminoglycan glycosylation, and that these modifications are important for proper multimerization. In agreement with this, neuronal cell lines deficient in O-glycosylation exhibit higher capacity for storing the neurotransmitter noradrenaline and enlarged neurotransmitter-containing dense core granules.