The inhibition of endocytosis affects HDL-lipid uptake mediated by the human scavenger receptor class B type I.
The scavenger receptor SR-BI plays an important role in the hepatic clearance of HDL cholesterol and other lipids, driving reverse cholesterol transport and contributing to protection against atherosclerosis in mouse models. We characterized the role of endocytosis in lipid uptake from HDL, mediated by the human SR-BI, using a variety of approaches to inhibit endocytosis, including hypertonic shock, potassium or energy depletion and disassembly of the actin cytoskeleton. Our studies revealed that unlike mouse SR-BI, human SR-BI-mediated HDL-lipid uptake was reduced by inhibition of endocytosis. This was not dependent on the cytoplasmic C-terminus of SR-BI. Monitoring the uptake of both the protein and lipid components of HDL revealed that although overall lipid uptake was decreased, the degree of selective lipid uptake was increased. These data suggest that that endocytosis is a dynamic regulator of SR-BI's selective lipid uptake activity.
Zhang
Yi
Y
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
Ahmed
Ayesha M
AM
Tran
Thu L
TL
Lin
Judy
J
McFarlane
Nicole
N
Boreham
Douglas R
DR
Igdoura
Suleiman A
SA
Truant
Ray
R
Trigatti
Bernardo L
BL
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D019921:Biotinylation; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016466:CHO Cells; D002460:Cell Line; D008076:Cholesterol, HDL / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D018955:CD36 Antigens; D008076:Cholesterol, HDL; D006982:Hypertonic Solutions; D007211:Indoles; D008075:Lipoproteins, HDL; D047428:Protein Kinase Inhibitors; D011993:Recombinant Fusion Proteins; C064758:Ro 31-8220; D000077191:Wortmannin