Logo of biochemjBJ Latest papers and much more!
Biochem J. 1997 Dec 1; 328(Pt 2): 635–642.
PMCID: PMC1218965

Formation of one or more intrachain disulphide bonds is required for the intracellular processing and transport of CD36.


In monocytes/macrophages, CD36 is thought to have a role as a scavenger receptor, mediating the phagocytosis of apoptotic cells and the endocytic uptake of oxidized low-density lipoproteins and fatty acids. The proposed topology of CD36 predicts that, of ten cysteine residues, six lie in the extracellular domain, whereas four are equally distributed in the two short terminal tails flanking the N-terminal and C-terminal hydrophobic stretches. Here we investigate the formation of intrachain disulphide bonds, on the basis of the assumption that the cysteine residues present in the luminal domains are generally oxidized, whereas those in the cytosol are reduced. As revealed by gel mobility-shift assays, disulphide bonds are present in the extracellular domain of the CD36 molecule. The formation of these bonds is required for the transport of CD36 from endoplasmic reticulum to Golgi. Furthermore reactive thiol groups are present in the CD36 sequence, which upon lysis form an intrachain extra loop as an artifact. This disulphide bond is not formed in either (1) truncated CD36 lacking the two C-terminal cysteine residues or (2) Triton X-100-insoluble wild-type CD36 molecules, suggesting that, in this fraction, the C-terminal thiol groups are modified.

Full Text

The Full Text of this article is available as a PDF (405K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Greenwalt DE, Lipsky RH, Ockenhouse CF, Ikeda H, Tandon NN, Jamieson GA. Membrane glycoprotein CD36: a review of its roles in adherence, signal transduction, and transfusion medicine. Blood. 1992 Sep 1;80(5):1105–1115. [PubMed]
  • Savill J, Hogg N, Ren Y, Haslett C. Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. J Clin Invest. 1992 Oct;90(4):1513–1522. [PMC free article] [PubMed]
  • Ren Y, Silverstein RL, Allen J, Savill J. CD36 gene transfer confers capacity for phagocytosis of cells undergoing apoptosis. J Exp Med. 1995 May 1;181(5):1857–1862. [PMC free article] [PubMed]
  • Ockenhouse CF, Tandon NN, Magowan C, Jamieson GA, Chulay JD. Identification of a platelet membrane glycoprotein as a falciparum malaria sequestration receptor. Science. 1989 Mar 17;243(4897):1469–1471. [PubMed]
  • Endemann G, Stanton LW, Madden KS, Bryant CM, White RT, Protter AA. CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem. 1993 Jun 5;268(16):11811–11816. [PubMed]
  • Nicholson AC, Frieda S, Pearce A, Silverstein RL. Oxidized LDL binds to CD36 on human monocyte-derived macrophages and transfected cell lines. Evidence implicating the lipid moiety of the lipoprotein as the binding site. Arterioscler Thromb Vasc Biol. 1995 Feb;15(2):269–275. [PubMed]
  • Abumrad NA, el-Maghrabi MR, Amri EZ, Lopez E, Grimaldi PA. Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36. J Biol Chem. 1993 Aug 25;268(24):17665–17668. [PubMed]
  • Pearson AM. Scavenger receptors in innate immunity. Curr Opin Immunol. 1996 Feb;8(1):20–28. [PubMed]
  • Oquendo P, Hundt E, Lawler J, Seed B. CD36 directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes. Cell. 1989 Jul 14;58(1):95–101. [PubMed]
  • Alessio M, Ghigo D, Garbarino G, Geuna M, Malavasi F. Analysis of the human CD36 leucocyte differentiation antigen by means of the monoclonal antibody NL07. Cell Immunol. 1991 Oct 15;137(2):487–500. [PubMed]
  • Calvo D, Vega MA. Identification, primary structure, and distribution of CLA-1, a novel member of the CD36/LIMPII gene family. J Biol Chem. 1993 Sep 5;268(25):18929–18935. [PubMed]
  • Vega MA, Seguí-Real B, García JA, Calés C, Rodríguez F, Vanderkerckhove J, Sandoval IV. Cloning, sequencing, and expression of a cDNA encoding rat LIMP II, a novel 74-kDa lysosomal membrane protein related to the surface adhesion protein CD36. J Biol Chem. 1991 Sep 5;266(25):16818–16824. [PubMed]
  • Acton SL, Scherer PE, Lodish HF, Krieger M. Expression cloning of SR-BI, a CD36-related class B scavenger receptor. J Biol Chem. 1994 Aug 19;269(33):21003–21009. [PubMed]
  • Franc NC, Dimarcq JL, Lagueux M, Hoffmann J, Ezekowitz RA. Croquemort, a novel Drosophila hemocyte/macrophage receptor that recognizes apoptotic cells. Immunity. 1996 May;4(5):431–443. [PubMed]
  • Hart K, Wilcox M. A Drosophila gene encoding an epithelial membrane protein with homology to CD36/LIMP II. J Mol Biol. 1993 Nov 5;234(1):249–253. [PubMed]
  • Daviet L, Buckland R, Puente Navazo MD, McGregor JL. Identification of an immunodominant functional domain on human CD36 antigen using human-mouse chimaeric proteins and homologue-replacement mutagenesis. Biochem J. 1995 Jan 1;305(Pt 1):221–224. [PMC free article] [PubMed]
  • Pearce SF, Wu J, Silverstein RL. A carboxyl terminal truncation mutant of CD36 is secreted and binds thrombospondin: evidence for a single transmembrane domain. Blood. 1994 Jul 15;84(2):384–389. [PubMed]
  • Tao N, Wagner SJ, Lublin DM. CD36 is palmitoylated on both N- and C-terminal cytoplasmic tails. J Biol Chem. 1996 Sep 13;271(37):22315–22320. [PubMed]
  • Tandon NN, Lipsky RH, Burgess WH, Jamieson GA. Isolation and characterization of platelet glycoprotein IV (CD36). J Biol Chem. 1989 May 5;264(13):7570–7575. [PubMed]
  • McGregor JL, Catimel B, Parmentier S, Clezardin P, Dechavanne M, Leung LL. Rapid purification and partial characterization of human platelet glycoprotein IIIb. Interaction with thrombospondin and its role in platelet aggregation. J Biol Chem. 1989 Jan 5;264(1):501–506. [PubMed]
  • Tsuji T, Osawa T. Purification and chemical characterization of human platelet membrane glycoprotein IV. J Biochem. 1986 Oct;100(4):1077–1085. [PubMed]
  • Fahey RC, Hunt JS, Windham GC. On the cysteine and cystine content of proteins. Differences between intracellular and extracellular proteins. J Mol Evol. 1977 Nov 25;10(2):155–160. [PubMed]
  • Hwang C, Sinskey AJ, Lodish HF. Oxidized redox state of glutathione in the endoplasmic reticulum. Science. 1992 Sep 11;257(5076):1496–1502. [PubMed]
  • Braakman I, Helenius J, Helenius A. Manipulating disulfide bond formation and protein folding in the endoplasmic reticulum. EMBO J. 1992 May;11(5):1717–1722. [PMC free article] [PubMed]
  • Valetti C, Sitia R. The differential effects of dithiothreitol and 2-mercaptoethanol on the secretion of partially and completely assembled immunoglobulins suggest that thiol-mediated retention does not take place in or beyond the Golgi. Mol Biol Cell. 1994 Dec;5(12):1311–1324. [PMC free article] [PubMed]
  • Reddy P, Sparvoli A, Fagioli C, Fassina G, Sitia R. Formation of reversible disulfide bonds with the protein matrix of the endoplasmic reticulum correlates with the retention of unassembled Ig light chains. EMBO J. 1996 May 1;15(9):2077–2085. [PMC free article] [PubMed]
  • Grassi F, Meneveri R, Gullberg M, Lopalco L, Rossi GB, Lanza P, De Santis C, Brattsand G, Buttò S, Ginelli E, et al. Human immunodeficiency virus type 1 gp120 mimics a hidden monomorphic epitope borne by class I major histocompatibility complex heavy chains. J Exp Med. 1991 Jul 1;174(1):53–62. [PMC free article] [PubMed]
  • Braakman I, Helenius J, Helenius A. Role of ATP and disulphide bonds during protein folding in the endoplasmic reticulum. Nature. 1992 Mar 19;356(6366):260–262. [PubMed]
  • Kosower NS, Kosower EM, Newton GL, Ranney HM. Bimane fluorescent labels: labeling of normal human red cells under physiological conditions. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3382–3386. [PMC free article] [PubMed]
  • Taylor KT, Tang Y, Sobieski DA, Lipsky RH. Characterization of two alternatively spliced 5'-untranslated exons of the human CD36 gene in different cell types. Gene. 1993 Nov 15;133(2):205–212. [PubMed]
  • Boussif O, Lezoualc'h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7297–7301. [PMC free article] [PubMed]
  • Alessio M, De Monte L, Scirea A, Gruarin P, Tandon NN, Sitia R. Synthesis, processing, and intracellular transport of CD36 during monocytic differentiation. J Biol Chem. 1996 Jan 19;271(3):1770–1775. [PubMed]
  • Lodish HF, Kong N. The secretory pathway is normal in dithiothreitol-treated cells, but disulfide-bonded proteins are reduced and reversibly retained in the endoplasmic reticulum. J Biol Chem. 1993 Sep 25;268(27):20598–20605. [PubMed]
  • Freedman RB. Protein disulfide isomerase: multiple roles in the modification of nascent secretory proteins. Cell. 1989 Jun 30;57(7):1069–1072. [PubMed]
  • Helenius A, Marquardt T, Braakman I. The endoplasmic reticulum as a protein-folding compartment. Trends Cell Biol. 1992 Aug;2(8):227–231. [PubMed]
  • Matsuno K, Diaz-Ricart M, Montgomery RR, Aster RH, Jamieson GA, Tandon NN. Inhibition of platelet adhesion to collagen by monoclonal anti-CD36 antibodies. Br J Haematol. 1996 Mar;92(4):960–967. [PubMed]
  • Lisanti MP, Scherer PE, Vidugiriene J, Tang Z, Hermanowski-Vosatka A, Tu YH, Cook RF, Sargiacomo M. Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: implications for human disease. J Cell Biol. 1994 Jul;126(1):111–126. [PMC free article] [PubMed]
  • Dorahy DJ, Lincz LF, Meldrum CJ, Burns GF. Biochemical isolation of a membrane microdomain from resting platelets highly enriched in the plasma membrane glycoprotein CD36. Biochem J. 1996 Oct 1;319(Pt 1):67–72. [PMC free article] [PubMed]
  • Stefanová I, Horejsí V, Ansotegui IJ, Knapp W, Stockinger H. GPI-anchored cell-surface molecules complexed to protein tyrosine kinases. Science. 1991 Nov 15;254(5034):1016–1019. [PubMed]
  • Shenoy-Scaria AM, Dietzen DJ, Kwong J, Link DC, Lublin DM. Cysteine3 of Src family protein tyrosine kinase determines palmitoylation and localization in caveolae. J Cell Biol. 1994 Jul;126(2):353–363. [PMC free article] [PubMed]
  • Sargiacomo M, Sudol M, Tang Z, Lisanti MP. Signal transducing molecules and glycosyl-phosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells. J Cell Biol. 1993 Aug;122(4):789–807. [PMC free article] [PubMed]
  • Rodgers W, Crise B, Rose JK. Signals determining protein tyrosine kinase and glycosyl-phosphatidylinositol-anchored protein targeting to a glycolipid-enriched membrane fraction. Mol Cell Biol. 1994 Aug;14(8):5384–5391. [PMC free article] [PubMed]
  • Brown DA, Rose JK. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell. 1992 Feb 7;68(3):533–544. [PubMed]
  • Rhinehart-Jones T, Greenwalt DE. A detergent-sensitive 113-kDa conformer/complex of CD36 exists on the platelet surface. Arch Biochem Biophys. 1996 Feb 1;326(1):115–118. [PubMed]
  • Alessio M, Greco NJ, Primo L, Ghigo D, Bosia A, Tandon NN, Ockenhouse CF, Jamieson GA, Malavasi F. Platelet activation and inhibition of malarial cytoadherence by the anti-CD36 IgM monoclonal antibody NL07. Blood. 1993 Dec 15;82(12):3637–3647. [PubMed]
  • Trezzini C, Jungi TW, Spycher MO, Maly FE, Rao P. Human monocytes CD36 and CD16 are signaling molecules. Evidence from studies using antibody-induced chemiluminescence as a tool to probe signal transduction. Immunology. 1990 Sep;71(1):29–37. [PMC free article] [PubMed]
  • Ockenhouse CF, Magowan C, Chulay JD. Activation of monocytes and platelets by monoclonal antibodies or malaria-infected erythrocytes binding to the CD36 surface receptor in vitro. J Clin Invest. 1989 Aug;84(2):468–475. [PMC free article] [PubMed]
  • Huang MM, Bolen JB, Barnwell JW, Shattil SJ, Brugge JS. Membrane glycoprotein IV (CD36) is physically associated with the Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7844–7848. [PMC free article] [PubMed]
  • Shattil SJ, Brugge JS. Protein tyrosine phosphorylation and the adhesive functions of platelets. Curr Opin Cell Biol. 1991 Oct;3(5):869–879. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...