Dynamic role of the transmembrane glycoprotein CD36 (SR-B2) in cellular fatty acid uptake and utilization

Jan F. C. Glatz, Joost J. F. P. Luiken
2018 Journal of Lipid Research  
This article is available online at http://www.jlr.org CD36 was reported to be the cellular receptor for thrombospondin (3), implicating a role of CD36 in irreversible platelet aggregation, as well as in the adherence of erythrocytes infected with the malaria parasite, Plasmodium falciparum, to the endothelium (4). Subsequently, it was discovered that CD36 is a macrophage receptor for oxidized LDL (oxLDL), thereby establishing its role as a scavenger receptor (5) , and that CD36 acts as
more » ... D36 acts as facilitator of membrane fatty acid transport (6). CD36 is currently known to be a member of a superfamily of scavenger receptor proteins (class B), which also includes scavenger receptor (SR)-B1 and lysosomal integral membrane protein-2 (LIMP-2). These three proteins share their structure, which comprises two transmembrane domains, a relatively large extracellular domain, and both the amino and carboxyl termini located within the cytoplasm (7). As a result, CD36 is now officially designated as SR-B2 (8). Human CD36 has recently been crystallized (9). The structure and proposed membrane topology of CD36 are schematically depicted in Fig. 1 . CD36 is not expressed ubiquitously, yet is present in a variety of mammalian cell types, including hematopoietic cells (platelets, monocytes, macrophages), endothelial cells, specialized epithelial cells in the breast and eye, enterocytes, and insulin-responsive cells, such as adipocytes, and cardiac and skeletal myocytes. This expression pattern is paralleled by a similar broad number of functions, which are, however, mostly related to the regulation of lipid metabolism and innate immunity. Specifically, CD36 is involved in inflammatory responses and atherothrombotic diseases, intestinal fat absorption, lipid storage in adipose tissue and lipid utilization by cardiac and skeletal muscle, metabolic disorders, such as obesity and diabetes, and Abstract The widely expressed transmembrane glycoprotein, cluster of differentiation 36 (CD36), a scavenger receptor class B protein (SR-B2), serves many functions in lipid metabolism and signaling. Here, we review CD36's role in facilitating cellular long-chain fatty acid uptake across the plasma membrane, particularly in heart and skeletal muscles. CD36 acts in concert with other membrane proteins, such as peripheral plasma membrane fatty acid-binding protein, and is an intracellular docking site for cytoplasmic fatty acid-binding protein. The cellular fatty-acid uptake rate is governed primarily by the presence of CD36 at the cell surface, which is regulated by the subcellular vesicular recycling of CD36 from endosomes to the plasma membrane. CD36 has been implicated in dysregulated fatty acid and lipid metabolism in pathophysiological conditions, particularly in high-fat diet-induced insulin resistance and diabetic cardiomyopathy. Current research is exploring signaling pathways and vesicular trafficking routes involving CD36 to identify metabolic targets to manipulate the cellular utilization of fatty acids. Because of its rate-controlling function in the use of fatty acids in the heart and muscle, CD36 would be a preferable target to protect myocytes against lipotoxicity. Despite a poor understanding of its mechanism of action, CD36 has emerged as a pivotal membrane protein involved in wholebody lipid homeostasis.-Glatz, J. F. C., and J. J. F. P. Luiken. Dynamic role of the transmembrane glycoprotein CD36 (SR-B2) in cellular fatty acid uptake and utilization. J. Lipid Res. 2018. 59: 1084-1093. Supplementary key words cluster of differentiation 36 • scavenger receptor B2 • heart • muscle Cluster of differentiation 36 (CD36) was first described in 1977 as glycoprotein IV (GP IIIb or GP IV), the fourth major band observed upon SDS-polyacrylamide gel electrophoresis of human platelet membranes (1). Ten years later, the protein was shown to be identical to the antigen recognized by monoclonal antibody OKM5, a marker for monocytes and macrophages and designated as the leukocyte differentiation antigen CD36 (2). In that same year, Abbreviations: CD36, cluster of differentiation 36; CPT-1, carnitine palmitoyltransferase-1; FABP c , cytoplasmic fatty acid-binding protein; FABP pm , plasma membrane fatty acid-binding protein; FAT, fatty acid translocase (putative) (CD36/SR-B2); FATP, fatty acid transport pro-
doi:10.1194/jlr.r082933 pmid:29627764 fatcat:ygietcqg4rci7hir74lshc3wii