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beta(2)-glycoprotein-1 (apolipoprotein H) and beta(2)-glycoprotein-1-phospholipid complex harbor a recognition site for the endocytic receptor megalin

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Item Type:Article
Title:beta(2)-glycoprotein-1 (apolipoprotein H) and beta(2)-glycoprotein-1-phospholipid complex harbor a recognition site for the endocytic receptor megalin
Creators Name:Moestrup, S.K. and Schousboe, I. and Jacobsen, C. and Leheste, J.R. and Christensen, E.I. and Willnow, T.E.
Abstract:Screening of serum by using a surface plasmon resonance analysis assay identified beta2-glycoprotein-I/apolipoprotein H as a plasma component binding to the renal epithelial endocytic receptor megalin. A calcium-dependent megalin-mediated beta2-glycoprotein-I endocytosis was subsequently demonstrated by ligand blotting of rabbit renal cortex and uptake analysis in megalin-expressing cells. Immunohistochemical and immunoelectron microscopic examination of kidneys and the presence of high concentrations of beta2-glycoprotein-I in urine of mice with disrupted megalin gene established that megalin is the renal clearance receptor for beta2-glycoprotein-I. A significant increase in functional affinity for purified megalin was observed when beta2-glycoprotein-I was bound to the acidic phospholipids, phosphatidylserine and cardiolipin. The binding of beta2-glycoprotein-I and beta2-glycoprotein-I- phospholipid complexes to megalin was completely blocked by receptor-associated protein. In conclusion, we have demonstrated a novel receptor recognition feature of beta2-glycoprotein-I. In addition to explaining the high urinary excretion of beta2-glycoprotein-I in patients with renal tubule failure, the data provide molecular evidence for the suggested function of beta2-glycoprotein-I as a linking molecule mediating cellular recognition of phosphatidylserine-exposing particles.
Keywords:beta 2-Glycoprotein I, Biosensing Techniques, Blood Proteins, Calcium, Cardiolipins, Cultured Tumor Cells, Endocytosis, Glycoproteins, Heymann Nephritis Antigenic Complex, Immunoelectron Microscopy, Immunohistochemistry, Immunologic Receptors, Kidney Cortex, Low Density Lipoprotein Receptor-Related Protein-1, Membrane Glycoproteins, Phosphatidylserines, Phospholipids, Protein Binding, Animals, Mice, Rabbits, Rats
Source:Journal of Clinical Investigation
Publisher:American Society for Clinical Investigation
Page Range:902-909
Date:1 September 1998
Official Publication:https://doi.org/10.1172/JCI3772
PubMed:View item in PubMed

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