The Influence of Particle Size and Multiple Apoprotein E-Receptor Interactions on the Endocytic Targeting of O3VLDL in Mouse Peritoneal Macrophages

. Low density lipoprotein (LDL) and (3-very low density lipoprotein (/3VLDL) are internalized by the same receptor in mouse peritoneal macrophages and yet their endocytic patterns differ; (3VLDL is targeted to both widely distributed and perinuclear vesicles, whereas LDL is targeted almost entirely to perinuclear lysosomes. This endocytic divergence may have important metabolic consequences since OVLDL is catabolized slower than LDL and is a more potent stimulator of aryl-CoA/cholesterol acyl transferase (ACAT) than LDL. The goal of this study was to explore the determinants of (3VLDL responsible for its pattern of endocytic targeting. Fluorescence microscopy experiments revealed that large, intestinally derived, apoprotein (Apo) E-rich /3VLDL was targeted mostly to widely distributed vesicles, whereas small, hepatically derived OVLDL was targeted more centrally (like LDL). Furthermore, the large /3VLDL had a higher ACATstimulatory potential than the smaller OVLDL. The basis for these differences was not due to fundamental differences in the means of uptake; L NDs and receptors internalized by receptor-mediated endocytosis may undergo a variety of cellular itin-eraries, including targeting of both ligand and receptor

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