The enigmatic membrane fatty acid transporter CD36: New insights into fatty acid binding and their effects on uptake of oxidized LDL.
The scavenger receptor CD36 binds numerous small biomolecules, including fatty acids, and even large ligands such as oxidized LDL, for which it is considered a receptor. Although CD36 has often been postulated to "transport" fatty acids across the plasma membrane, fatty acids translocation (mass transport or kinetics) was not affected by expression of CD36 in HEK293 cells; however, esterification of fatty acids (cellular uptake) was increased. These recent results from our lab are consistent with the established mechanism of fatty acid entry into cells by passive diffusion (flip-flop) and also with the well-documented enhancement of uptake of fatty acids by CD36 in other cell types. A fascinating new discovery is that CD36 has multiple fatty acid binding sites on the extracellular domain of CD36. As illuminated by new methodologies that we have applied, these sites have high affinity and exhibit rapid exchange with the medium. In an initial study of functional consequences of binding, several dietary fatty acids enhanced uptake of oxidized LDL into HEK293 cells expressing CD36. This is the first established link between physical binding of fatty acids and a function of CD36, and has implications for obesity and atherosclerosis. New methods as those used in our study could also be applied to elucidate other functional roles of fatty acid binding to CD36.
Department of Physiology & Biophysics, Boston University School of Medicine, Boston, MA 02118, United States; Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, United States.
Anthony G
AG
Jay
Department of Physiology & Biophysics, Boston University School of Medicine, Boston, MA 02118, United States. Electronic address: jhamilt@gmail.com.
James A
JA
Hamilton
D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport; D018955:CD36 Antigens / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism* / Q000473:pathology; D004951:Esterification; D005227:Fatty Acids / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000473:pathology
D018955:CD36 Antigens; C000628671:CD36 protein, human; D005227:Fatty Acids; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein
Fatty acid; Lipid uptake; Low-density lipoprotein; Surface plasmon resonance; Transport CD36