20 years after the identification of megalin as the podocyte target antigen of nephritogenic antibodies in HN, we identified the human counterpart of megalin, the enzymatic podocyte antigen neutral endopeptidase (NEP).
Pathogenic antigens involved in the induction of Heymann nephritis (HN), an experimental rat model of human membranous nephritis, have been identified in megalin (gp330) and the receptor-associated protein (RAP) [1,2].
Previously, it was reported that the second ligand-binding domain (LBD II) of megalin is involved in the pathogenesis of passive HN because it is capable of binding antibodies in vivo and initiating formation of immune deposits (ID).
This review considers what is now known about the structure, function, and trafficking of megalin and RAP and the role of these two molecules in the pathogenesis of HN.
Autoantibodies from the kidneys of rats with Heymann nephritis reacted with a nonglycosylated segment of GP330 that contains cysteine-rich 40-amino acid repeats, which are also features of the LDL receptor.