Details

Autor(en) / Beteiligte

• Klassen, R. Bryan S
• Allen, Patricia L
• Batuman, Vecihi
• Crenshaw, Kimberly
• Hammond, Timothy G

Titel

Light chains are a ligand for megalin

Ist Teil von

• Journal of applied physiology (1985), 2005-01, Vol.98 (1), p.257-263

Ort / Verlag

Bethesda, MD: Am Physiological Soc

Erscheinungsjahr

2005

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 1 Department of Chemistry, Xavier University, 2 Tulane University School of Medicine, Tulane/Veterans Affairs Environmental Astrobiology Center, and 3 New Orleans Veterans Affairs Medical Center, New Orleans, Louisiana Submitted 8 October 2003 ; accepted in final form 23 July 2004 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 - and -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. cubilin; cancer; flow cytometry Address for reprint requests and other correspondence: R. B. Klassen, Dept. of Chemistry, Box 114-B, Xavier Univ. of Louisiana, 1 Drexel Dr., New Orleans, LA 70125-1098 (E-mail: bklassen{at}xula.edu )