[Vesicular flow in epithelial cells: physiopathologic importance of two multiligand receptors].

Epithelial structures lining the proximal tubule and the yolk sac are characterized by a high rate of internalization followed by degradation of the proteins exposed to their apical pole. This function implies the expression by these epithelia of specialized proteins which have the ability to bind numerous ligands and/or lysosomal targeting properties. An improved knowledge of these molecules is needed since their expression in a limited number of epithelia may account for the specificity of some pathologies induced in particular by toxins. This paper deals with two such "candidate" proteins, gp330/megalin and gp280 which have been expressed in all species studied. gp280 is the target of teratogenic antibodies and is identified here as the receptor for intrinsic factor-cobalamin complexes but in all likelihood also binds other ligands. Antibodies to gp280 markedly stimulate the fusion of renal endosomes suggesting that it may play a role in targeting processes. gp330/megalin has been recently identified as the ligand of polybasic compounds such as gentamicin and is a key component in the internalization of the drug by tubular cells leading to renal toxicity. gp330/megalin also intervenes in endosomal fusion and some of its toxic properties may be mediated by this route.

Duke Scholars

Author Timothy Grant Hammond Medicine, Nephrology