Journal
JOURNAL OF APPLIED PHYSIOLOGY
Volume 98, Issue 1, Pages 257-263Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.01090.2003
Keywords
cubilin; cancer; flow cytometry
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Funding
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR017659] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R29DK046117] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [S11ES009996] Funding Source: NIH RePORTER
- NCRR NIH HHS [P20 RR 017659] Funding Source: Medline
- NIDDK NIH HHS [DK 46117] Funding Source: Medline
- NIEHS NIH HHS [ES 09996] Funding Source: Medline
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Cubilin and megalin are giant glycoprotein receptors abundant on the luminal surface of proximal tubular cells of the kidney. We showed previously that light chains are a ligand for cubilin. As cubilin and megalin share a number of common ligands, we further investigated the ligand specificity of these receptors. Three lines of evidence suggest that light chains can also bind megalin: 1) anti-megalin antiserum largely displaces brush-border light chain binding and megalin-expressing BN-16 cell uptake more than anti-cubilin antiserum, 2) direct binding studies on isolated proteins using surface plasmon resonance techniques confirm that megalin binds light chains, and 3) light chains compete with known megalin ligands for brush-border membrane binding and BN-16 cell uptake. The megalin-light chain interaction is divalent ion dependent and similar for both kappa- and lambda-light chains. A fit of the data on light chain binding to megalin over a concentration range 0.078 - 2.5 mg/ml leads to an estimated dissociation constant of 6 x 10(-5) M, corresponding approximately to one light chain-binding site per megalin and in the same range for dissociation constants for cubilin binding. These data suggest that light chains bind the tandem megalin-cubilin complex. Megalin is the major mediator of light chain entry into megalin-expressing membrane such as the apical surface of proximal tubular epithelial cells.
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