Lipoprotein Receptors in Extraembryonic Tissues of the Chicken

Abstract

Yolk is the major source of nutrients for the developing chicken embryo, but molecular details of the delivery mechanisms are largely unknown. During oogenesis in the chicken, the main yolk components vitellogenin and very low density lipoprotein (VLDL) are taken up into the oocytes via a member of the low density lipoprotein receptor gene family termed LR8 (Bujo, H., Hermann, 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 accompanied by partial degradation of the yolk precursor protein moieties; however, 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; the 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 allantois, the embryo's catabolic sink. Stored yolk VLDL interacts with LR8 localized on the surface of the yolk sac endodermal endothelial cells (EEC), is internalized, and degraded, as demonstrated by the catabolism of fluorescently labeled VLDL in cultured EEC. Addition to the incubation medium of the 39-kDa receptor-associated protein, which inhibits all known LR8/ligand interactions, blocks the uptake of VLDL by EEC. The levels of endogenous receptor-associated protein correspond to those of LR8؉ but not LR8؊, suggesting that it may play a role in the modulation of surface presentation of LR8؉. Importantly, EEC express significant levels of microsomal triglyceride transfer protein and protein disulfide isomerase, key components required for lipoprotein synthesis. Because the apolipoprotein pattern of VLDL isolated from the yolk sac-efferent omphalomesenteric vein is very different from that of yolk VLDL, these data strongly suggest that embryo plasma VLDL is resynthesized in the EEC. LR8 is a key mediator of a two-step pathway, which affects the uptake of VLDL from the yolk sac and the subsequent delivery of its components to the growing embryo.The developing avian embryo constitutes an excellent system for the study of lipid and lipoprotein transport phenomena. The yolk, accumulated via uptake from the circulation of precursor proteins during the vitellogenic phase of oocyte growth (1), serves as the sole source of lipid, carbohydrate, and protein. Interestingly, only 350 mg of the 5-6 g of lipid in the yolk are mobilized during the first 2 weeks of embryogenesis; the major portion is transported during the final week. Such uptake, to a large part, occurs via the yolk sac (2), which utilizes the yolk lipoprotein components, following their degradation or modification, for resynthesis of lipoproteins that are subsequently secreted and delivered to the embryo through the embryonic circulatory system. The chick yolk sac is characterized by an outer layer of loosely associated mese...

3-Hydroxy-3-Methylglutaryl CoA Reductase Inhibitor Retards Chicken Embryonic Growth

“…Yolk VLDL contains apolipoprotein (apo) B fragments, cathepsin D-catalyzed intraoocytic proteolysis of apoB-100. In contrast, intact apoB-100, which is a major apo of VLDL in the hen, was present in the circulating VLDL of the embryo M. Sat0 and M. Furuse (Hermann et al, 2000). These data show that VLDL in the embryonic circulation seems to result from de nouo synthesis rather than directly from the yolk.…”

“…In fact, the VLDL fraction provides Yolk VLDL binds t o the low density lipoprotein receptor (LDLR) family member termed LR8, which is expressed in the extraembryonic yolk sac and mobilizes yolk for utilization by the embryo. Stored yolk VLDL interacts with LR8 localized on the surface of the yolk sac endodermal endothelial cells and is internalized (Hermann et al, 2000). These results indicate that members of LDLR family play important roles in lipid metabolism and growth of the chicken embryo.…”

“…ApoB-100 is stored in the yolk VLDL in partial proteolytic cleavage product. In contrast, VLDL in embryonic circulation contains intact apoB-100 suggesting that apoB-100 is synthesized in the embryo (Hermann et al, 2000). It was reported that inhibition of HMG-CoA reductase by atorvastatin decreases VLDL apoB production in miniature pigs (Burnett et al, 1997).…”

The Developing Chicken Yolk Sac Acquires Nutrient Transport Competence by an Orchestrated Differentiation Process of Its Endodermal Epithelial Cells

“…The ligand binding domains of cubilin and LRP2 recognize a vast number of diverse proteins, many of which are yolk constituents, such as protein-bound vitamins, hormones, and a range of lipoproteins (28). Furthermore, we have previously shown that the YS EECs also express LR8 (the galline homologue of the mammalian VLDL receptor), which is capable of internalizing apoB-containing lipoproteins, such as VLDL (22), expanding the list of receptors involved in the uptake of yolk precursor macromolecules into the EECs.…”

Molecular cloning of the two very low-density lipoprotein receptor (VLDLR) subtypes in geese and the effect of overfeeding on their MRNA levels

“…These results indicate that the O-linked domain may play an important role in the affinity between the receptors and their ligands. The role of VLDLR II in lipid metabolism was less obvious than for VLDLR I, and it is supposed to participate in other metabolic processes (Hermann et al 2000;May et al 2002May et al , 2003b. Their tissue expression pattern and capability to bind and internalize the lipoproteins of the two VLDLR subtypes indicate that the expression level of the two subtypes correspond to the activity of lipid metabolism in different tissues.…”