Distinct mechanisms for OxLDL uptake and cellular trafficking by class B scavenger receptors CD36 and SR-BI.
Modified forms of LDL, including oxidized low density lipoprotein (OxLDL), contribute to macrophage lipid accumulation in the vessel wall. Despite the pathophysiological importance of uptake pathways for OxLDL, the molecular details of OxLDL endocytosis by macrophages are not well understood. Studies in vitro demonstrate that the class B scavenger receptor CD36 mediates macrophage uptake and degradation of OxLDL. Although the closely related scavenger receptor class B type I (SR-BI) binds OxLDL with high affinity, evidence that SR-BI plays a role in OxLDL metabolism is lacking. In this study, we directly compared OxLDL uptake and degradation by CD36 and SR-BI. Our results indicate that although CD36 and SR-BI internalize OxLDL, SR-BI mediates significantly less OxLDL degradation. Endocytosis of OxLDL by both SR-BI and CD36 is independent of caveolae, microtubules, and actin cytoskeleton. However, OxLDL uptake by CD36, but not SR-BI, is dependent on dynamin. The analysis of chimeric SR-BI/CD36 receptors shows that the CD36 C-terminal cytoplasmic tail is necessary and sufficient for dynamin-dependent OxLDL internalization by class B scavenger receptors. These findings indicate that different mechanisms are involved in OxLDL uptake by SR-BI and CD36, which may segregate these two structurally homologous receptors at the cell surface, leading to differences in intracellular trafficking and degradation.
Sun
Bing
B
Graduate Center for Nutritional Sciences, University of Kentucky Medical Center, Lexington, KY 40536, USA.
Boyanovsky
Boris B
BB
Connelly
Margery A
MA
Shridas
Preetha
P
van der Westhuyzen
Deneys R
DR
Webb
Nancy R
NR
D000199:Actins / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D018955:CD36 Antigens / Q000378:metabolism*; D019556:COS Cells; D021941:Caveolae / Q000378:metabolism; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D051381:Rats; D014168:Transferrin / Q000378:metabolism
D000199:Actins; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D014168:Transferrin; C099252:oxidized low density lipoprotein; D034281:Dynamins