An intrinsic mechanism of secreted protein aging and turnover

Significance In the blood, secreted proteins have different life spans that determine their abundance and function. Measurements of plasma protein composition and biological activities remain important for many clinical diagnoses. However the molecular mechanisms by which secreted proteins age and turnover have remained unidentified. The findings of this research have established an intrinsic and constitutive mechanism of secreted protein aging and turnover. This mechanism involves multiple factors including circulating glycosidases that progressively remodel the N-glycan linkages attached to most secreted proteins. N-glycan remodeling with time exposes glycan ligands of various endocytic lectin receptors that then eliminate these aged secreted proteins. This mechanism thereby determines the life spans and abundance of secreted proteins, and modulates the pathogenesis and outcomes of disease.