ArticleProceedings of the National Academy of Sciences of the United States of America2015
An intrinsic mechanism of secreted protein aging and turnover.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The contribution of the sinusoidal endothelial cell receptors CLEC4M, stabilin-2, and SCARA5 to VWF-FVIII clearance in thrombosis and hemostasis.Journal of thrombosis and haemostasis : JTH · 2023Pooled it
- Combating ageing beyond the cell: Emerging roles of extracellular proteostasis.The FEBS journal · 2026Review
- Site-specific profiling of structure and function of Igµ B cell receptor glycans.Nature communications · 2026Article
- Platelet aging and desialylation increase apoptotic priming and BCL-XCell death & disease · 2026Article
- Mrc1 (MMR, CD206) controls the blood proteome in reducing inflammation, age-associated organ dysfunction and mortality in sepsis.Nature communications · 2025Article
- Endothelial Glycocalyx Turnover in Vascular Health and Disease: Rethinking Endothelial Dysfunction.Annual review of biochemistry · 2025Review
- Compositional and topological determinants of a physiological Ashwell-Morell receptor ligand.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- MYO18B promotes lysosomal exocytosis by facilitating focal adhesion maturation.The Journal of cell biology · 2025Article
- IgA displays site- and subclass-specific glycoform differences despite equal glycoenzyme expression.Cell communication and signaling : CCS · 2025Article
- Engineering of anticancer human immunoglobulin A equipped with albumin for enhanced plasma half-life.PNAS nexus · 2025Article
- Advances and challenges in plant N-glycoengineering: when fucosylation matters.Frontiers in plant science · 2025Review
- Asialoglycoprotein receptor 1: a multifaceted receptor in the liver and cardiovascular system.Frontiers in medicine · 2025Review
- ASGR1 deficiency improves atherosclerosis but alters liver metabolism in ApoECardiovascular diabetology · 2024Article
- O-glycan determinants regulate VWF trafficking to Weibel-Palade bodies.Blood advances · 2024Article
- ASGR1 deficiency diverts lipids toward adipose tissue but results in liver damage during obesity.Cardiovascular diabetology · 2024Article
- Sialic acids on T cells are crucial for their maintenance and survival.Frontiers in immunology · 2024Article
- Therapeutic potential to target sialylation and SIGLECs in neurodegenerative and psychiatric diseases.Frontiers in neurology · 2024Review
- Neuraminidase inhibition improves endothelial function in diabetic mice.American journal of physiology. Heart and circulatory physiology · 2023Article
- Sialic acid O-acetylation patterns and glycosidic linkage type determination by ion mobility-mass spectrometry.Nature communications · 2023Article
- Article
7 more citing papers are in PubMed but not listed here.
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6 authors.
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Abstract
The composition and functions of the secreted proteome are controlled by the life spans of different proteins. However, unlike intracellular protein fate, intrinsic factors determining secreted protein aging and turnover have not been identified and characterized. Almost all secreted proteins are posttranslationally modified with the covalent attachment of N-glycans. We have discovered an intrinsic mechanism of secreted protein aging and turnover linked to the stepwise elimination of saccharides attached to the termini of N-glycans. Endogenous glycosidases, including neuraminidase 1 (Neu1), neuraminidase 3 (Neu3), beta-galactosidase 1 (Glb1), and hexosaminidase B (HexB), possess hydrolytic activities that temporally remodel N-glycan structures, progressively exposing different saccharides with increased protein age. Subsequently, endocytic lectins with distinct binding specificities, including the Ashwell-Morell receptor, integrin αM, and macrophage mannose receptor, are engaged in N-glycan ligand recognition and the turnover of secreted proteins. Glycosidase inhibition and lectin deficiencies increased protein life spans and abundance, and the basal rate of N-glycan remodeling varied among distinct proteins, accounting for differences in their life spans. This intrinsic multifactorial mechanism of secreted protein aging and turnover contributes to health and the outcomes of disease.
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