Uptake of oxidized low density lipoprotein by CD36 occurs by an actin-dependent pathway distinct from macropinocytosis.
The class B scavenger receptor CD36 has numerous ligands that include modified forms of low density lipoprotein, fibrillar amyloid, apoptotic cells, and Plasmodium falciparum-infected red blood cells, linking this molecule to atherosclerosis, Alzheimer disease, malaria, and other diseases. We studied the signaling events that follow receptor engagement and lead to CD36 and ligand internalization. We show that oxidized low density lipoprotein or antibody-induced clustering of CD36 triggers macropinocytosis and internalization of the receptor-ligand complex. Remarkably, however, CD36 internalization is independent of macropinocytosis and occurs by a novel endocytic mechanism that depends on actin, but not dynamin. This actin-driven endocytosis requires the activation Src family kinases, JNK, and Rho family GTPases, but, unlike macropinocytosis, it is not affected by inhibitors of phosphatidylinositol 3-kinase or Na/H exchange. Manipulation of this unique mode of internalization may prove helpful in the prevention and management of the wide range of diseases in which CD36 is implicated.
Collins
Richard F
RF
Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Touret
Nicolas
N
Kuwata
Hirotaka
H
Tandon
Narendra N
NN
Grinstein
Sergio
S
Trimble
William S
WS
D000199:Actins / Q000378:metabolism*; D018955:CD36 Antigens / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D010873:Pinocytosis; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D019061:src-Family Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020741:rho GTP-Binding Proteins