Lipoprotein receptors in extraembryonic tissues of the chicken

Yolk is the major source of nutrients for the developing chicken embryo, bu t molecular details of the delivery mechanisms are largely unknown. During oogenesis in the chicken, the main yolk components vitellogenin and very lo w density lipoprotein (VLDL) are taken up into the oocytes via a member of the low density lipoprotein receptor gene family termed LR8 (Bujo, H., Herm ann, M., Kaderli, M. O., Jacobsen, L., Sugawara, S., Nimpf, J., Yamamoto, T ., and Schneider, W.J. (1994) EMBO J. 13, 5165-5175). This endocytosis is a ccompanied by partial degradation of the yolk precursor protein moieties; h owever, fragmentation does not abolish binding of VLDL to LR8. The receptor exists in two isoforms that differ by a so-called O-linked sugar domain; t he shorter form (LR8-) is the major form in oocytes, and the longer protein (LR8+) predominates in somatic cells. Here we show that both LR8 isoforms are expressed at ratios that vary with embryonic age in the extraembryonic yolk sac, which mobilizes yolk for utilization by the embryo, and in the al lantois, the embryo's catabolic sink. Stored yolk VLDL interacts with LR8 l ocalized on the surface of the yolk sac endodermal endothelial cells (EEC), is internalized, and degraded, as demonstrated by the catabolism of fluore scently labeled VLDL, in cultured EEC. Addition to the incubation medium of the 39-kDa receptor-associated protein, which inhibits all known LR8/ligan d interactions, blocks the uptake of VLDL by EEC. The levels of endogenous receptor-associated protein correspond to those of LR8+ but not LR8-, sugge sting that it may play a role in the modulation of surface presentation of LR8+. Importantly, EEC express significant levels of microsomal triglycerid e transfer protein and protein disulfide isomerase, key components required for lipoprotein synthesis. Because the apolipoprotein pattern of VLDL isol ated from the yolk sac-efferent omphalomesenteric vein is very different fr om that of yolk VLDL, these data strongly suggest that embryo plasma VLDL i s resynthesized in the EEC. LR8 is a key mediator of a two-step pathway, wh ich affects the uptake of VLDL from the yolk sac and the subsequent deliver y of its components to the growing embryo.