The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake.
Neutrophil-gelatinase-associated lipocalin (NGAL) is a prominent protein of specific granules of human neutrophils also synthesized by epithelial cells during inflammation. NGAL binds bacterial siderophores preventing bacteria from retrieving iron from this source. Also, NGAL may be important in delivering iron to cells during formation of the tubular epithelial cells of the primordial kidney. No cellular receptor for NGAL has been described. We show here that megalin, a member of the low-density lipoprotein receptor family expressed in polarized epithelia, binds NGAL with high affinity, as shown by surface plasmon resonance analysis. Furthermore, a rat yolk sac cell line known to express high levels of megalin, endocytosed NGAL by a mechanism completely blocked by an antibody against megalin.
Hvidberg
Vibeke
V
Institute of Medical Biochemistry, University of Aarhus, Denmark.
Jacobsen
Christian
C
Strong
Roland K
RK
Cowland
Jack B
JB
Moestrup
Søren K
SK
Borregaard
Niels
N
D000209:Acute-Phase Proteins / Q000378:metabolism*; D004705:Endocytosis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance
D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D007501:Iron