CD36, a Scavenger Receptor Involved in Immunity, Metabolism, Angiogenesis, and Behavior

By R. Silverstein, M. Febbraio. Science Signaling, 2009

1,181 citations recorded by the source corpus.

Signaling by CD36 is ligand and cell specific and is implicated in multiple human diseases. CD36 is a multifunctional cell-surface receptor present on many cell types, including platelets, mononuclear phagocytes, and muscle, fat, and gut cells. It is conserved in mammals, and there are many invertebrate orthologs. CD36 binds to several major classes of ligands, including the matrix protein thrombospondin, long-chain fatty acids, and oxidized phospholipids and lipoproteins; in different contexts, it serves to regulate angiogenesis, innate immune responses, fatty acid metabolism, and sensory responses to fatty acids. CD36 signaling is mediated by activation of specific intracellular pathways that may include kinases of the Src family and mitogen-activated protein kinases. Because of the importance of CD36 signaling in human diseases, including atherosclerosis, thrombosis, Alzheimer’s disease, obesity, diabetes, and cancer, these signaling pathways are under intense scrutiny. This Review includes two figures and 123 citations. CD36 is a membrane glycoprotein present on platelets, mononuclear phagocytes, adipocytes, hepatocytes, myocytes, and some epithelia. On microvascular endothelial cells, CD36 is a receptor for thrombospondin-1 and related proteins and functions as a negative regulator of angiogenesis. On phagocytes, through its functions as a scavenger receptor recognizing specific oxidized phospholipids and lipoproteins, CD36 participates in internalization of apoptotic cells, certain bacterial and fungal pathogens, and modified low-density lipoproteins, thus contributing to inflammatory responses and atherothrombotic diseases. CD36 also binds long-chain fatty acids and facilitates their transport into cells, thus participating in muscle lipid utilization, adipose energy storage, and gut fat absorption and possibly contributing to the pathogenesis of metabolic disorders, such as diabetes and obesity. On sensory cells, CD36 is involved in insect pheromone signaling and rodent fatty food preference. The signaling pathways downstream of CD36 involve ligand-dependent recruitment and activation of nonreceptor tyrosine kinases, specific mitogen-activated protein kinases, and the Vav family of guanine nucleotide exchange factors; modulation of focal adhesion constituents; and generation of intracellular reactive oxygen species. CD36 in many cells is localized in specialized cholesterol-rich membrane microdomains and may also interact with other membrane receptors, such as tetraspanins and integrins. Identification of the precise CD36 signaling pathways in specific cells elicited in response to specific ligands may yield novel targets for drug development.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/ba0da8c1ae8d60e97c15ef52b575b72c852d4f6f

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Citations in the corpus

Genetic determinants of the gut microbiome in UK Twins (2016, neutral): “CD36 is involved in a variety of functions, including long chain fatty acid tasting on the tongue (Silverstein and Febbraio, 2009).”
The interaction of hepatic lipid and glucose metabolism in liver diseases. (2012, background): “activity, which has also been identified to facilitate FA uptake [34,35].”
Memory CD8+ T cells use cell intrinsic lipolysis to support the metabolic programming necessary for development (2014, background): “For lipid uptake, in vitro or ex vivo cells were incubated with either 1 mM Bodipy FL C16 or 10 mg/ml Bodipy FL LDL in TCM.”
Carcinoma-associated fibroblasts: orchestrating the composition of malignancy (2016, background): “CD36 is a widely expressed protein that modulates cell type-specific and ligand-specific functions, including adipocyte differentiation, angiogenesis, apoptosis, transforming growth factor-β (TGF-β) activation, cell– ECM interactions, and immune signaling (Silverstein and Febbraio 2009).”
The Metabolic Signature of Macrophage Responses (2019, background): “On the other side, the main sources of fatty acids in M2 derive from uptake via the scavenger receptormediated pathway (157) and through lysosomal lipolysis mediated by lysosomal acid lipase, all these pathways being up-regulated upon IL-4 stimulation (147).”
CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation (2013, background): “In the AD brain and diabetic pancreas, amyloid plaques arise from the aggregation of pre-fibrillar amyloidogenic peptides such as the Aβ(1-42) peptide17, 18, 19 or IAPP20, 21, 22, which oligomerize and give rise to higher order structures, including fibrils.”
Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease (2018, background): “The fatty acid translocase protein, CD36, facilitates the transport of long-chain fatty acids and is regulated by peroxisome proliferator-activated receptor (PPAR) γ, pregnane X receptor, and liver X receptor [21].”