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

Abstract

The widely expressed transmembrane glycoprotein 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 (FABP pm ), and is an intracellular docking site for cytoplasmic fatty acid-binding protein (FABP c ). 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 ratecontrolling 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 whole-body lipid homeostasis. 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 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, thereby establishing its role as a scavenger receptor (5), and that CD36 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 B1 (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 now officially is designated as scavenger receptor B2 (SR-B2) (8).Human CD36 has recently been crystallized (9). The structure and proposed membrane topology of CD36 are schematically depicted in Fig. 1 (10)). Interestingly, CD36 is also expressed in human taste bud cells where it functions as a f...

Connecting pancreatic islet lipid metabolism with insulin secretion and the development of type 2 diabetes

“…27,28 CD36/SR-B2 is a class B scavenger receptor that shows high affinity for long-chain FA. 29 CD36 is considered to concentrate FA within specific plasma membrane domains and increase fatty acid availability for subsequent membrane translocation. Several studies have shown that CD36 increases fatty acid uptake in beta cells.…”

Lipid Transfer Proteins: Introduction to the Thematic Review Series

“…The transport of these fatty acids into the requiring tissues is facilitated by the fatty acid transporter CD36 present in the plasma membrane. This role of CD36 is reviewed by Glatz and colleagues (8). CD36 is a member of the family of class B scavenger receptors (SRB-2).…”

Administration of Fenofibrate Markedly Elevates Fabp3 in Rat Liver and Plasma and Confounds Its Use as a Preclinical Biomarker of Cardiac and Muscle Toxicity

“…One such transporter examined is the fatty‐acid translocase or cluster of differentiation 36 ( Cd36 ) classified as a scavenger receptor class B protein (SR‐B2). This fatty‐acid transporter has been found not to be well expressed in the liver and appears to be much more readily expressed in other energy‐utilizing tissues like heart and adipose tissues (Glatz and Luiken, ). However, upon treatment with fenofibrate, the hepatic mRNA levels of Cd36 were significantly increased (Lee et al, ).…”