ArticleGlycobiology2015
Identification of a fourth mannose 6-phosphate binding site in the cation-independent mannose 6-phosphate receptor.
Article in Glycobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Glycan-based biological degraders targeting the cytokine immune axis.Communications biology · 2026Article
- Design of Potent Mannose-6-Phosphate Derivatives as Ligands for CI-M6P/IGF2R Using Fluorescence Polarization Assay.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Production of Domain 9 from the cation-independent mannose-6-phosphate receptor fused with an Fc domain.Glycoconjugate journal · 2024Article
- Comparative study on incorporation of three recombinant human α-galactosidase A drugs (agalsidases) into cultured fibroblasts and organs/tissues of Fabry mice.Molecular genetics and metabolism reports · 2024Article
- StaufenC facilitates utilization of the ERAD pathway to transport dsRNA through the endoplasmic reticulum to the cytosol.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The host mannose-6-phosphate pathway and viral infection.Frontiers in cellular and infection microbiology · 2024Review
- Development of Oligomeric Mannose-6-phosphonate Conjugates for Targeted Protein Degradation.ACS medicinal chemistry letters · 2023Article
- Mannose-6-phosphate glycan for lysosomal targeting: various applications from enzyme replacement therapy to lysosome-targeting chimeras.Animal cells and systems · 2022Article
- Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate.Scientific reports · 2021Article
- Insulin-Like Growth Factor 2 As a Possible Neuroprotective Agent and Memory Enhancer-Its Comparative Expression, Processing and Signaling in Mammalian CNS.International journal of molecular sciences · 2021Review
- Two Distinct Lysosomal Targeting Strategies Afford Trojan Horse Antibodies With Pan-Filovirus Activity.Frontiers in immunology · 2021Article
- The Potential of Proteolytic Chimeras as Pharmacological Tools and Therapeutic Agents.Molecules (Basel, Switzerland) · 2020Review
- Surface plasmon resonance analysis of complex formation of therapeutic recombinant lysosomal enzymes with domain 9 of human cation-independent mannose 6-phosphate receptor.Molecular genetics and metabolism reports · 2020Article
- Allosteric regulation of lysosomal enzyme recognition by the cation-independent mannose 6-phosphate receptor.Communications biology · 2020Article
- The mannose 6-phosphate/insulin-like growth factor 2 receptor mediates plasminogen-induced efferocytosis.Journal of leukocyte biology · 2019Article
- Insulin-Like Growth Factor-II/Cation-Independent Mannose 6-Phosphate Receptor in Neurodegenerative Diseases.Molecular neurobiology · 2017Review
- Article
- Lysosomal and vacuolar sorting: not so different after all!Biochemical Society transactions · 2016Review
- Article
- Glycan microarrays of fluorescently-tagged natural glycans.Glycoconjugate journal · 2015Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The 300 kDa cation-independent mannose 6-phosphate receptor (CI-MPR) plays an essential role in lysosome biogenesis by targeting ∼ 60 different phosphomannosyl-containing acid hydrolases to the lysosome. This type I membrane glycoprotein has a large extracellular region comprised of 15 homologous domains. Two mannose 6-phosphate (M6P) binding sites have been mapped to domains 3 and 9, whereas domain 5 binds preferentially to the phosphodiester, M6P-N-acetylglucosamine (GlcNAc). A structure-based sequence alignment predicts that the C-terminal domain 15 contains three out of the four conserved residues identified as essential for carbohydrate recognition by domains 3, 5 and 9 of the CI-MPR, but lacks two cysteine residues that are predicted to form a disulfide bond. To determine whether domain 15 of the CI-MPR has lectin activity and to probe its carbohydrate-binding specificity, truncated forms of the CI-MPR were tested for binding to acid hydrolases with defined N-glycans in surface plasmon resonance analyses, and used to interrogate a phosphorylated glycan microarray. The results show that a construct encoding domains 14-15 binds both M6P and M6P-GlcNAc with similar affinity (Kd = 13 and 17 μM, respectively). Site-directed mutagenesis studies demonstrate the essential role of the conserved Tyr residue in domain 15 for phosphomannosyl binding. A structural model of domain 15 was generated that predicted an Arg residue to be in the binding pocket and mutagenesis studies confirmed its important role in carbohydrate binding. Together, these results show that the CI-MPR contains a fourth carbohydrate-recognition site capable of binding both phosphomonoesters and phosphodiesters.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.