Light-chain binding sites on renal brush-border membranes.
Immunoglobulin light chains are low-molecular-weight proteins filtered at the renal glomerulus and catabolized within the proximal tubular epithelium. Excessive production and urinary excretion of light chains are associated with renal dysfunction. They also interfere with proximal renal tubule epithelial functions in vitro. We studied the binding of 125I-labeled kappa- and lambda-light chains, obtained from the urine of multiple myeloma patients, to rat and human renal proximal tubular brush-border membranes. Light-chain binding to brush borders was also demonstrated immunologically by flow cytometry. Computer analysis of binding data was consistent with presence of a single class of low-affinity, high-capacity, non-cooperative binding sites with relative selectivity for light chains on both rat and human kidney brush-border membranes. The dissociation constants of light chains ranged from 1.6 X 10(-5) to 1.2 X 10(-4) M, and maximum binding capacity ranged from 4.7 +/- 1.3 X 10(-8) to 8.0 +/- 0.9 X 10(-8) (SD) mol/mg protein at 25 degrees C. Kappa- and lambda-light chains competed with each other for binding with comparable affinity constants. Competition by albumin and beta-lactoglobulin, however, was much weaker, suggesting relative site selectivity for light chains. These binding sites probably function as endocytotic receptors for light chains and possibly other low-molecular-weight proteins.
Batuman
V
V
Medical Service, Veterans Administration Medical Center, East Orange 07019.
Dreisbach
A W
AW
Cyran
J
J
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D013696:Temperature
D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007457:Iodine Radioisotopes