CD36 GPIV (platelet glycoprotein IV),GPIIIb,OKM5 antigen, PASIV
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 2 span
Erythroid Cell
Platelet
Macrophage
Endothelial Cell
Dendritic Cell
Monocyte
B Cell
85 / 85
88 / 88
113 / 113

Expression
CD36 is expressed on platelets, mature monocytes and macrophages, microvascular endothelial cells, mammary endothelial cells, pancreatic β cells, during stages of erythroid cell development and on some macrophage derived dendritic cells.  In the mouse, CD36 is expressed on B cells.


Structure
MOLECULAR FAMILY NAME:  Belongs to the scavenger receptor superfamily.

CD36 is a multi-pass type-3 2 span 471 aa glycoprotein.  It contains an extracellular domain which contains 10 N-linked and 1 O-linked heavily glycosylation sites, 2 hydrophobic transmembrane domains and cytoplasmic domains resulting in a N- and C-terminal tails which are palmitoylated.  CD36 is a member of a superfamily that includes the receptor for a high density lipoprotein SR-BI, known as CLA-1, the lysosomal protein LIMP II, and the Drosophila epithelial molecule Emp.  CD36 mRNA exhibits considerable size heterogeneity as a result of alternate splicing of 5'-untranslated and 3'-untranslated exons.  In addition, skipping of coding exons 4 and 5, in an erythroleukemia cell line, generates a CD36 isoform of 57 kD.  CD36 has been proposed as a candidate gene through which the transcription factor Oct-2 could affect B cell differentiation in the mouse.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Platelets 88 kDa / 113 kDa
Fetal erythrocytes 78 kDa
Mammary epithelial cells 85 kDa
Erythroleukemic 88 kDa, 85 kDa, 57 kDa
HeLa 85 kDa, (160) kDa 85 kDa
Dermal microvascular endothelial cells 80-90 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yeilds 2 different mRNA isoforms.  The first is expressed in HEL cells and omits 41 aa-143 aa residues.  The 2nd has not yet been translated but in which the last 89 aa residues have been omitted.

POST-TRANSLATIONAL MODIFICATION

CD36 is purported to be heavily glycosylated, with 10 N-linked glycosylation sites in the extracellular portion. Glycosylation has been suggested to confer its resistance to proteolytic cleavage.  Threonine 92 has been shown to be phosphorylated.  CD36 is also palmitoylated on both N- and C-terminal cytoplasmic tails.

Ligands
A number of different ligands have been identified for CD36.  The ligands include the extracellular matrix components of collagen I, IV and V and thrombospondin, oxidized low density lipoprotein, fatty acids, anionic phospholipids, Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and bacterial diacyl glycerides.  CD36 associates noncovalently with the Src family protein tyrosine kinases Fyn, Lyn and Yes.

LIGANDS AND MOLECULES ASSOCIATED WITH CD36
Molecule Comment
Oxidized low density lipoprotein Ligand
Long chain fatty acids Ligand
Anionic phospholipids Ligand
Collagen types I, IV and V Ligand
Thrombospondin Ligand
Plasmodium falciparum infected erythrocytes Ligand


Intracellular signaling is probably associated with phosphorylation of Fyn, Lyn and Yes, but the manner by which the cytoplasmic tail interacts with these PTKs is unknown.



Function
CD36 is a multifunctional glycoprotein.  CD36 is the receptor for thrombospondin.  On macrophages it functions in the phagocytic clearance of apoptotic cells and is thought to involve interaction of CD36 with thrombospondin collagen I, IV and V.  CD36 has a role in platelet-collagen adhesion and aggregation, platelet monocyte and platelet tumor cell interaction.  It is a scavenger receptor for oxidized low density lipoprotein (LDL) and shed phot-receptor out segments and is involved in recognition and phagocytosis of apoptotic cells and a part in atherogenesis.  It is a signal transducer and appears to transduce signals through its association with Src family protein tyrosine kinases.  CD36 appears to transduce signals through its associated Src family protein tyrosine kinases.  Following ligand binding, a signal transduction cascade is initiated which can activate platelets and leads to an oxidative burst in platelets and macrophages.  On adipocytes, CD36 is involved in the binding and transport into the cell of long-chain fatty acids.  CD36 is involved in cytoadherence of P. falciparum malaria infected erythrocytes and as a endothelial cell receptor for PfEMP1.  A large antigenically variant malarial protein is expressed on the surface of parasitized erythrocytes.  CD36 also has a role in the innate immune system, binding immune bacterial diacyl glycerides and presenting them to TLR2 and TLR6.

BIOCHEMICAL ACTIVITY

CD36 activity recognizes an oxidized low density lipoprotein, long chain fatty acids, anionic phospholipids, collagen types I, IV and V, thrombospondin (TSP) and P. falciparum infected erythrocytes and recognizes apoptotic neutrophils in cooperation with TSP and avb 3.  Other ligands may still be unknown.

DISEASE RELEVANCE AND FUNCTION OF CD36 IN INTACT ANIMAL

CD36 interacts with fatty acid translocase of pancreatic β cells and mediates fatty acid effects on insulin secretion.  Patients with type-1 and type-2 diabetes have an upregulated CD36 expression on macrophages during hyperglycemia and is associated with atherosclerotic lesions.  Murine model of diabetes suggests increased expression of CD36 in renal proximal tubular cells renders them more suscpetible to apoptosis.  Mutations in CD36 cause platelet glycoprotein deficiency.

Atherogenesis: There is attachment to the vessel wall, infiltration and macrophages foam cell formation. In malaria cytoadherence of infected cells to microvascular endothelial cells is an important factor in the virulence of cerebral malaria.

Inflammation: There is resolution of inflammation by phagocytosis of aged PMN.

Vision: CD36-mediated phagocytosis of rod outer segment cells is thought to be critical for normal visual function.

CD36 deficiency: Naka-negative individuals do not express CD36 on their platelets, a type I variant, or on their platelets and monocytes, a type II variant.  This may be predominantly due to a Pro90 to Ser substitution mutation, but as yet no physiological problems have been associated with this deficiency.


Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD36
Molecule Comment
Oct-2 The first gene shown to be regulated by the Oct-2 transcription factor during B cell differentiation
PEBP2 The PEBP2/CBF transcription factors may be important for the constitutive expression of CD36 in monocyte
CBF The PEBP2/CBF transcription factors may be important for the constitutive expression of CD36 in monocyte

SUBSTRATES

It may be possible that CD36 regulates autophosphorylation of residue Thr92.

ENZYMES WHICH MODIFY CD36

It may be possible that Thr92 is phosphorylated by extracellular threonine kinase(s).

ADDITIONAL INSIGHTS

The physiological events regulated by CD36 ligation are still very much unknown. Up to 50% of oxidized LDL are ingested through CD36, thus CD36 appears to be a major scavenger receptor. However, given the apparent absence of disease states in CD36 deficient subjects, other mechanisms appear to be capable of compensating for its absence.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 948P16671
MouseQ08857L23108
RatQ07969L19658
Antibodies
CB38   View Reactivity

Revised June 25, 2008


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