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Top left, Receptor-mediated uptake and intracellular processing of triglyceride-rich remnants and cholesteryl ester-rich LDL in rat liver (1988 version), showing passage of lipoproteins through fenestrae in the sinusoidal endothelium, followed by binding to endocytic receptors (Y) on hepatocytic microvilli projecting into the space of Disse (SD). The endocytic receptors migrate with their cargo to coated pits at the microvillar bases where they undergo endocytosis to form primary endosomes. After loss of the clathrin coat and endosome-fusion, the lipoproteins dissociate from the receptors at the acidic pH within the endosome. The lipoproteins are transported within the maturing endosomes toward the biliary (apical) pole of the cells, forming multivesicular bodies (MVB) (late endosomes), whereas the excess surface membrane resulting from endosome-fusion forms recycling endosomes that carry the receptors back to the basolateral surface of the cell (modified from Figure 1 in Havel RJ, Hamilton RL. Hepatocytic lipoprotein receptors and intracellular lipoprotein catabolism. Hepatology. 1988;8:1689–1704.). Top right (2003 version), Enlargement of a basolateral microvillus and adjacent endothelial cell (E), showing that chylomicron and large VLDL remnants pass through endothelial cell-fenestrae to the space of Disse where they bind initially to proteoglycan-bound apo E and hepatic lipase as well as LDLR, all of which are anchored to the microvillar membrane. Proteoglycan-bound hepatic lipase binds and hydrolyzes remnant-lipids, increasing exposure of the endocytic receptor-binding domain of apo E. Hepatic lipase can also act as a ligand for the endocytic receptors. Additional proteoglycan-bound apo E on microvilli acquired by the remnants increases the affinity of the remnant particles for LRP. The extent to which proteoglycans, hepatic lipase, and surface apo E themselves undergo endocytosis with the remnant particles is unknown. Normally, the surface density of LRP greatly exceeds that of LDLR, but only LDLR can readily bind remnants without further modification in the space of Disse. Bottom left, Thin section electron micrograph of normal rat liver illustrating the basolateral surface of hepatocytes (H) projecting numerous microvilli into the space of Disse. Plasma, including lipoproteins up to  200 nm diameter in the sinusoid, exchanges freely with the space of Disse through fenestrae (arrows) in the endothelium (E). x18 000 diameters. Bottom right, Ultracryothin section of normal rat hepatocyte space of Disse showing microvilli decorated with 5-nm colloidal gold complexed with affinity-purified rabbit polyclonal anti-LRP from rat liver.10 x90 000 diameters.
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