Cd36Edit
CD36 is a multifunctional transmembrane glycoprotein that operates at the intersection of metabolism, immunity, and vascular biology. Encoded by the CD36 gene, the protein is also known as glycoprotein IV on platelets and functions as a prominent member of the scavenger receptor family. It is expressed in a variety of tissues, including adipose tissue, macrophages, endothelial cells, platelets, and taste receptor cells, where it contributes to lipid handling, inflammatory signaling, angiogenesis, and the perception of dietary fats.
CD36 binds an unusually wide range of ligands, reflecting its diverse roles. Ligands include oxidized low-density lipoprotein (oxLDL), long-chain fatty acids, collagen, thrombospondin-1, and other matrix components. This broad binding profile enables CD36 to mediate uptake of fatty acids into cells, scavenging of modified lipoproteins by macrophages, recognition of damaged tissue, and signaling events that influence inflammation and metabolism. The protein is a class B scavenger receptor and forms dimers and higher-order oligomers on the cell surface, with its large extracellular domain responsible for ligand engagement. Intracellular signaling partners, including kinases from the src-family, link ligand binding to downstream cellular responses. For a broader context, see scavenger receptor and lipid metabolism.
CD36 exists as a two-transmembrane-domain receptor with a substantial extracellular loop that constitutes the primary ligand-binding surface. The gene is located on chromosome 7 in humans, and the protein has multiple post-translational glycosylation sites that influence its localization and function. Its expression is finely tuned according to tissue type and metabolic state, which helps explain why CD36 can contribute to both normal physiology and disease when dysregulated. See also glycoprotein IV and Plasmodium falciparum in the context of disease interactions.
Structure
Gene and protein architecture
CD36 is a transmembrane glycoprotein comprising two short cytoplasmic tails separated by two transmembrane domains, with a large extracellular loop that carries most ligand-binding activity. The protein is heavily glycosylated, which affects folding, stability, and surface expression. It forms monomers, dimers, and higher-order oligomers, enabling cooperative binding to ligands. The intracellular regions couple to signaling pathways, including kinases that coordinate metabolic and inflammatory responses. See glycoprotein IV and src family kinases for deeper connections to structure and signaling.
Expression patterns
CD36 is abundant in adipocytes and macrophages, where it mediates fatty acid uptake and scavenging of modified lipids, respectively. It is also present on endothelial cells and platelets, contributing to vascular biology and hemostasis, and on taste receptor cells in the tongue, where it participates in the detection of dietary fats. See adipose tissue, macrophage, endothelial cell, platelet, and taste receptor cells for related topics.
Functions
Lipid uptake and metabolism
In adipose tissue and muscle, CD36 facilitates the uptake of long-chain fatty acids, influencing energy balance and lipid storage. This activity links CD36 to overall metabolic homeostasis and to disorders such as obesity and insulin resistance when dysregulated. See lipid metabolism and fatty acids for the broader framework.
Oxidized LDL uptake and foam cell formation
In macrophages, CD36 mediates the uptake of oxidized LDL, contributing to foam cell development and the progression of atherosclerotic lesions. This role places CD36 at the forefront of discussions about cardiovascular risk and the inflammatory components of vascular disease. See oxLDL and foam cell for related mechanisms, and atherosclerosis for disease context.
Immune recognition and inflammation
CD36 participates in innate immune recognition and the clearance of cellular debris, linking metabolism to inflammatory signaling. Its activity can amplify inflammatory pathways in certain contexts, while also contributing to tissue repair processes in others. See innate immunity and macrophage for broader immune connections.
Angiogenesis and vascular biology
CD36 interacts with anti-angiogenic ligands such as thrombospondin-1 (TSP-1), which can inhibit neovascularization in certain settings. This function has implications for tumor biology and wound healing, where angiogenesis needs to be tightly regulated. See thrombospondin-1 and angiogenesis for related topics.
Taste perception
In the tongue, CD36 functions as a fatty acid receptor that influences the palatability and sensory detection of dietary fats, contributing to feeding behavior and energy intake. See taste receptor and gustation for broader perspectives on taste biology.
Clinical significance
Metabolic and cardiovascular disease
CD36's involvement in fatty acid uptake and oxLDL handling connects it to metabolic syndrome, obesity, insulin resistance, and type 2 diabetes mellitus. Its activity in macrophages and adipocytes can influence foam cell formation and hepatic lipid accumulation, with potential consequences for atherosclerosis and nonalcoholic fatty liver disease (NAFLD). The net effect of CD36 on cardiovascular risk is nuanced, as both protective and detrimental influences can arise depending on tissue context and metabolic state. See type 2 diabetes mellitus, NAFLD, and atherosclerosis for connected topics.
Infectious diseases
CD36 participates in host–pathogen interactions, including malaria pathogenesis, where parasite-infected erythrocytes leverage CD36 to adhere to vascular endothelium in some disease manifestations. This topic sits at the intersection of metabolism and infectious disease biology. See Plasmodium falciparum and malaria for broader background.
Genetic variation
Genetic variation in CD36 influences receptor expression and function, with potential effects on fatty acid uptake, inflammatory responses, and disease susceptibility. Patterns of variant frequency differ across populations, underscoring the importance of considering ancestry in biomedical research without resorting to simplistic genetic determinism. See population genetics and racial disparities in health for related considerations.
Controversies and debates
Therapeutic targeting versus physiological necessity: Because CD36 participates in essential processes such as fatty acid uptake and innate immunity, strategies that broadly inhibit CD36 carry the risk of unintended energetic deficits, dyslipidemia, or immune dysregulation. Proponents of targeted or tissue-specific approaches argue for precision therapies that modulate CD36 activity only where pathology is driven by its maladaptive functions, while preserving normal physiology. See therapeutic targeting and drug development (in relation to receptor biology).
Role in atherosclerosis and metabolic disease: The contribution of CD36 to foam cell formation and plaque development is clear in many model systems, but human atherogenesis is multifactorial. Critics caution against overemphasizing a single receptor as a dominant driver; advocates highlight CD36 as a modifiable node within a network of receptors that coordinate lipid handling and inflammation. See atherosclerosis and foam cell for additional context.
Genetic variation and population health: Differences in allele frequencies across populations prompt careful interpretation of association studies. While some variants are linked with altered fatty acid uptake or inflammatory responses, translating these findings into broad public health recommendations requires nuance to avoid deterministic messaging about race or ethnicity. See population genetics and racial disparities in health for more discussion.
Policy implications and innovation: From a policy standpoint, encouraging private-sector research and translational programs to exploit CD36 biology may accelerate new therapies, but this must be balanced with rigorous safety testing and rigorous oversight to prevent premature or poorly targeted interventions. See biomedical ethics and drug safety for related policy discussions. Regarding critiques that aim to dismiss gene-centered research as ideologically motivated, a measured view holds that robust scientific evidence and patient outcomes—not political rhetoric—should guide development.