The Human Scavenger Receptor CD36

Abstract

Human CD36 is a class B scavenger receptor expressed in a variety of cell types such as macrophage and adipocytes. This plasma membrane glycoprotein has a wide range of ligands including oxidized low density lipoprotein and long chain fatty acids which involves the receptor in diseases such as atherosclerosis and insulin resistance. CD36 is heavily modified posttranslationally by N-linked glycosylation, and 10 putative glycosylation sites situated in the large extracellular loop of the protein have been identified; however, their utilization and role in the folding and function of the protein have not been characterized. Using mass spectrometry on purified and peptide N-glycosidase F-deglycosylated CD36 and also by comparing the electrophoretic mobility of different glycosylation site mutants, we have determined that 9 of the 10 sites can be modified by glycosylation. Flow cytometric analysis of the different glycosylation mutants expressed in mammalian cells established that glycosylation is necessary for trafficking to the plasma membrane. Minimally glycosylated mutants that supported trafficking were identified and indicated the importance of carboxyl-terminal sites Asn-247, Asn-321, and Asn-417. However, unlike SRBI, no individual site was found to be essential for proper trafficking of CD36. Surprisingly, these minimally glycosylated mutants appear to be predominantly core-glycosylated, indicating that mature glycosylation is not necessary for surface expression in mammalian cells. The data also show that neither the nature nor the pattern of glycosylation is relevant to binding of modified low density lipoprotein.Human CD36, originally identified in platelets as glycoprotein IV (1), is a class B scavenger receptor localized to the plasma membrane. It is not expressed ubiquitously but is present in a variety of different cells and tissue types including epithelial cells (2), macrophages (3), endothelial cells of the microvasculature (4), and smooth muscle (5). Its function is complex, and its involvement in different disease scenarios, such as cancer (6), atherosclerosis (3,7,8), malaria (9), and insulin resistance (10), most likely reflects the interaction of the receptor with a particular ligand in a specific cell type. For example, CD36 expressed in monocytic macrophages functions as a scavenger receptor for the uptake of oxidized LDL 2 (3, 11). Under certain physiological conditions, this results in the lipid loading of macrophages at the site of tissue damage in the arterial wall, leading to foam cell formation and plaque development, a key early stage in the pathogenesis of atherosclerosis (8,12). In fat and muscle cells, CD36 plays an essential role in lipid homeostasis by uptake of long chain fatty acids (13). In this case CD36 deficiency has been linked to disorders in lipid metabolism, giving rise to increased incidences of insulin resistance and cardiomyopathies (11,14,15).Although much is known about the function of CD36, less is known about its structure. CD36 has no bacterial homologues but is...

Identification of Inhibitors of CD36-Amyloid Beta Binding as Potential Agents for Alzheimer’s Disease

“…Although not rigorously tested, our data and those from others also suggest that the N-glycosylation of the CD36, at least in the extracellular portion, is not required to retain the binding capacity to Aβ 27 . Interestingly, the N-glycosylation of the CD36 ectodomain was not found to be important for the surface expression or the binding activity to modified low-density lipoproteins 28 .…”

Genetic deletion of CD36 enhances injury after acute neonatal stroke

“…CD36 is central to several aspects of microglia/macrophage function, including migratory activity of these cells and production of inflammatory mediators 32, 33 . We therefore anticipated that the number of Iba1 + cells would be unchanged and the cells would be smaller in CD36ko.…”

Select membrane proteins modulate MNV-1 infection of macrophages and dendritic cells in a cell type-specific manner

“…Another example is dengue virus-1, which uses CD209 to infect dendritic cells, while the high-affinity laminin receptor mediates dengue virus-1 infection of liver cells (Navarro-Sanchez et al, 2003; Thepparit and Smith, 2004). Differential protein usage by MNV-1 on different cell types may also be driven by changes in glycosylation patterns since the four glycoproteins analyzed in the current study have multiple glycosylation sites, whose glycosylation pattern can change depending on the cell type (Bartolazzi et al, 1996; Goodman et al, 2010; Hoosdally et al, 2009; Powlesland et al, 2009). Future studies are needed to confirm a role for differential glycosylation in cell-type specific receptor usage by MNV and to identify the cell-type specific function of these proteins during MNV infection.…”