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Related Experiment Videos

Light chains are a ligand for megalin.

R Bryan S Klassen1, Patricia L Allen, Vecihi Batuman

  • 1Dept. of Chemistry, Box 114-B, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125-1098, USA. bklassen@xula.edu

Journal of Applied Physiology (Bethesda, Md. : 1985)
|August 3, 2004
PubMed
Summary

Light chains bind to both cubilin and megalin receptors in kidney proximal tubules. Megalin is identified as the primary receptor mediating light chain entry into these cells.

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Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Cubilin and megalin are large glycoprotein receptors found on kidney proximal tubule cells.
  • Previous research identified light chains as a ligand for cubilin.
  • Cubilin and megalin share several common ligands, prompting further investigation into their specificity.

Purpose of the Study:

  • To investigate the ligand specificity of cubilin and megalin receptors.
  • To determine if light chains also bind to the megalin receptor.
  • To elucidate the role of megalin in light chain uptake by kidney cells.

Main Methods:

  • Utilized anti-megalin and anti-cubilin antisera to assess ligand displacement.
  • Employed surface plasmon resonance for direct binding studies of isolated proteins.

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  • Conducted competition assays using known megalin ligands for binding and cellular uptake.

    • Main Results:

    • Anti-megalin antiserum significantly displaced light chain binding and uptake, more so than anti-cubilin antiserum.
    • Direct binding studies confirmed that megalin binds to light chains.
    • Light chains competed with known megalin ligands, indicating shared binding pathways and a dissociation constant of 6 x 10(-5) M for megalin-light chain interaction.

    Conclusions:

    • Light chains bind to both cubilin and megalin, likely as a tandem complex.
    • Megalin is the principal receptor mediating the entry of light chains into megalin-expressing cells, such as proximal tubular epithelial cells.
    • This interaction is dependent on divalent ions and occurs similarly for both kappa- and lambda-light chains.