COMPARATIVE IMMUNOCHEMISTRY AND ONTOGENY OF 2 CLOSELY RELATED COATED PIT PROTEINS - THE 280-KD TARGET OF TERATOGENIC ANTIBODIES AND THE 330-KD TARGET OF NEPHRITOGENIC ANTIBODIES

We bave previously shown that monoclonal antibodies specific for a 280 -kd protein (gp280) concentrated within the coated pits of renal and y olk sac brush border-induced fetal malformations, whereas antibodies s pecific for gp330, another coated pit protein with a similar distribut ion, bad no deleterious effect on embryonic development. In this study , we show that gp280 and gp330 are closely related proteins, as indica ted by 1) similarities in peptide maps obtained after cyanogen bromide cleavage, 2) immunological cross-reactivity related to a minor contin gent of antibodies that do not bave teratogenic activity, and 3) async hronous but related expressions during ontogenesis. During the early s tages of development, the expression of the two glycoproteins was limi ted to (gp330) or predominant in (gp280) the clathrin-coated pits and intermicrovillar areas. In the pre-implantation embryo, gp330 was expr essed by trophectodermal cells, which became negative in day-6 embryos trapped in endometrial infoldings. At this stage, gp280 and gp330 wer e both simultaneously detectable at the apical pole of the first entob lastic cells and remained expressed by the brush border of visceral yo lk sac epithelial cells until the end of pregnancy. In addition, gp330 was expressed by amniotic cells and neurectodermal structures. During nephrogenesis, in contrast, the expression of gp280 and gp330 by the intermicrovillar areas of the proximal tubule cell was the result of a complex maturation process. gp280 and gp330 were diffusely distribute d in S-shaped bodies in the presumptive areas of the glomerulus, proxi mal tubule, and distal tubule (gp330). During development of the nephr on, the pattern of expression became progressively restricted to the p roximal tubule and glomerulus (gp330), and selective localization in t he intermicrovillar areas was only achieved in filtrating nephrons.