Identification of a Functional Site on CD36 Involved in the Interaction Between Platelets and Collagen

Abstract

Adhesion of platelets to collagen, exposed on the subendothelium as a result of vessel wall injury, is a vital step in the formation of a haemostatic plug. Glycoprotein CD36, also known as GPIIIb/GPIV, is one of the platelet glycoproteins known to interact with collagen. The aim of this work was to identify structural/functional sites on CD36 interacting with collagen. Eight peptides, corresponding to sites presumed to be hydrophylic, were synthesized by Fmoc (Fluorenylmethoxycarbonyl) chemistry. Peptides were tested for their ability to inhibit platelet aggregation induced by type I collagen. Peptide E5 (WLNETGTIGDEKA; 415-427), but not the other peptides, inhibited aggregation and secretion of washed platelets induced by collagen but had no effect on thrombin or ADP induced aggregation. Moreover, peptide E5 was shown to interfere with the binding of (125)I-labelled CD36 to collagen. Peptide E5 had little or no effect on collagen-induced platelet aggregation performed in platelet rich plasma (PRP), as previously described in the cases of monoclonal antibodies directed against α(2)or β(1). These results indicate that peptide E5 represents a site on CD36 that interacts with collagen and is involved in platelet functions.

Osteogenic Potential of Caspases Related to Endochondral Ossification

“…The apparent downregulation of CD36 demonstrated by PCR Arrays was confirmed by pan caspase inhibition in cultured ulnae, where the expression of CD36 was maintained in controls but was strongly decreased in treated samples. CD36 functions as a receptor for collagens, 24,25 trombospondin, 26 and oxidized low-density lipoprotein. 27 CD36 is suggested to be involved in bone resorption by activation of c-src signaling in osteoclasts.…”

Variability of theCD36 gene in West Africa

“…The N-and C-terminal ends (spanning residues 16 and 467472, respectively) appear to be cytoplasmic, while residues 35439 constitute a large extracellular domain, which is highly glycosylated [Vega et al, 1991;Oquendo et al, 1989]. Ligand-binding domains have been mapped to amino acid positions 93 120 for thrombospondin, to 2893 and possibly 120155 for oxidized low density lipoprotein (ox-LDL) [Pearce et al, 1995[Pearce et al, , 1998, to 415 427 for collagen [Mercier et al, 1995], and to 821, 97110, 145171, and 146164 for P. falciparum-infected erythrocytes [Asch et al, 1993;Baruch et al, 1999].…”