Cyclophilin B binding to platelets supports calcium-dependent adhesion to collagen.
We have recently reported that cyclophilin B (CyPB), a secreted cyclosporine-binding protein, could bind to T lymphocytes through interactions with two types of binding sites. The first ones, referred to as type I, involve interactions with the conserved domain of CyPB and promote the endocytosis of surface-bound ligand, while the second type of binding sites, termed type II, are represented by glycosaminoglycans (GAG). Here, we further investigated the interactions of CyPB with blood cell populations. In addition to lymphocytes, CyPB was found to interact mainly with platelets. The binding is specific, with a dissociation constant (kd) of 9 +/- 3 nmol/L and the number of sites estimated at 960 +/- 60 per cell. Platelet glycosaminoglycans are not required for the interactions, but the binding is dramatically reduced by active cyclosporine derivatives. We then analyzed the biologic effects of CyPB and found a significant increase in platelet adhesion to collagen. Concurrently, CyPB initiates a transmembranous influx of Ca(2+) and induces the phosphorylation of the P-20 light chains of myosin. Taken together, the present results demonstrate for the first time that extracellular CyPB specifically interacts with platelets through a functional receptor related to the lymphocyte type I binding sites and might act by regulating the activity of a receptor-operated membrane Ca(2+) channel.
Laboratoire de Chimie Biologique, Unité Mixte de Recherche no. 8576 du CNRS, Université des Sciences et Technologies de Lille, Villeneuve d'Ascq, France.
F
F
Allain
S
S
Durieux
A
A
Denys
M
M
Carpentier
G
G
Spik
D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D003094:Collagen; D021983:Cyclophilins; D006801:Humans; D020104:Immunophilins / Q000378:metabolism*; D019696:Peptidylprolyl Isomerase; D010973:Platelet Adhesiveness; D011485:Protein Binding; D015398:Signal Transduction
C081786:cyclophilin B; D003094:Collagen; D021983:Cyclophilins; D020104:Immunophilins; D019696:Peptidylprolyl Isomerase; D002118:Calcium