Regulation of circulating mannosylated proteome by macrophage mannose receptor, Mrc1

Abundance of secreted proteins is tightly regulated in circulation, and its dysregulation forms a basis for development of pathology. N-glycosylation has been shown to be a decisive factor in determining the half-life of these proteins. Exoglycosidases remodel the proteins and exposure of cryptic ligands of endocytic lectin receptors determine their half-lives. We have devised a strategy for non-denaturing enrichment of these mannosylated proteins upon Mrc1 lectin receptor deficiency. Data-independent acquisition mass spectrometry was used to quantify these proteins post-enrichment by mannose-binding lectin (Concanavalin A). We find ligand profile of Mrc1 comprises of over 200 proteins, linking inflammation, organ dysfunction and sepsis to turnover of mannosylated blood proteome. Mannosylated proteome was profiled in mouse plasma upon Mrc1 knock-out and in human plasma upon sepsis. Pathway enrichment was performed to draw parallels between Mrc1 deficiency in mice and sepsis in human.