Deep quantitative glycoproteomics reveals gut microbiome induced remodeling of the brain glycoproteome

ABSTRACT: Protein glycosylation is a highly diverse post-translational modification, modulating key cellular processes such as cell signaling, adhesion and cell-cell interactions. Its deregulation has been associated with various pathologies, including cancer and neurological diseases. Methods capable of quantifying glycosylation dynamics are essential to start unraveling the biological functions of protein glycosylation. Here we present Deep Quantitative Glycoprofiling (DQGlyco), a method that combines high-throughput sample preparation, high-sensitivity detection, and precise multiplexed quantification of protein glycosylation. We used DQGlyco to profile the mouse brain glycoproteome, in which we identify more than 200,000 unique N-glycopeptides - this amounts to 25-fold more glycopeptides identified compared to previous studies. We observed extensive heterogeneity of glycoforms and determined their functional and structural preferences. We used our quantitative approach to map surface-exposed glycoforms as well as to characterize glycosites tissue-specificity. The presence of a defined gut microbiota resulted in extensive remodeling of the brain glycoproteome when compared to that of germ-free animals, exemplifying how the gut microbiome may affect brain protein functions.

INSTRUMENT(S): Orbitrap Fusion Lumos, Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Brain, Liver, Permanent Cell Line Cell, Kidney

SUBMITTER: Clement Potel  

LAB HEAD: Mikhail M. Savitski

PROVIDER: PXD052447 | Pride | 2025-02-07

REPOSITORIES: pride