EPITHELIAL GLYCOPROTEIN-330 MEDIATES ENDOCYTOSIS OF PLASMINOGEN ACTIVATOR-PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 COMPLEXES

Epithelial glycoprotein 330 (gp330) is structurally similar to the mul tifunctional alpha2-macroglobulin receptor/low density lipoprotein rec eptor-related protein (alpha2MR/LRP). gp330 and alpha2MR/LRP bind Ca2 with high affinity, and both receptors bind and mediate endocytosis O f alpha2MR-associated protein (RAP). In the present report, we describ e that affinity-purified gp330 from rabbit renal cortex binds plasmino gen activator inhibitor type-1 (PAI-1) complexed with urokinase-type p lasminogen activator (uPA). Alpha2M-methylamine, which binds with high affinity to alpha2MR/LRP, did not bind to gp330. The apparent K(d) fo r binding of uPA.PAI-1 complexes was about 0.8 nM at 4-degrees-C. The binding was calcium-dependent and inhibited by recombinant RAP (rRAP) and tissue type plasminogen activator-PAI-1 complexes. Thin sections o f rabbit renal proximal tubules bound I-125-labeled uPA.PAI-1 and rRAP in the apical part of proximal tubules corresponding to the localizat ion of gp330. The binding of I-125-uPA.PAI-1 complexes in tubules was abolished by excess unlabeled rRAP, and a rRAP-inhibitable endocytosis and degradation of labeled uPA.PAI-1 complexes was demonstrated by pe rfusion of isolated rabbit proximal tubules. The results establish an endocytotic function of gp330 and suggest that gp330 is an important c omponent of the fibrinolytic system in gp330-containing epithelia as f ound in, for example, kidney and lung.