Light chains are a ligand for megalin.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Klassen, RBS; Allen, PL; Batuman, V; Crenshaw, K; Hammond, TG

Published Date

  • January 2005

Published In

Volume / Issue

  • 98 / 1

Start / End Page

  • 257 - 263

PubMed ID

  • 15286052

Pubmed Central ID

  • 15286052

International Standard Serial Number (ISSN)

  • 8750-7587

Digital Object Identifier (DOI)

  • 10.1152/japplphysiol.01090.2003


  • eng

Conference Location

  • United States