Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface.
Activated platelets bind numerous adhesive and procoagulant proteins by receptor-mediated processes. Although there is little evidence to suggest that these processes are heterogeneous in platelets, we previously found that platelets co-stimulated with collagen and thrombin express functional alpha-granule factor V only on a subpopulation of cells. Here we show that these cells, referred to as 'COAT-platelets', bind additional alpha-granule proteins, including fibrinogen, von Willebrand factor, thrombospondin, fibronectin and alpha2-antiplasmin. These proteins are all transglutaminase substrates, and inhibitors of transglutaminase prevent the production of COAT-platelets. A synthetic transglutaminase substrate (CP15) also binds to COAT-platelets, and analysis by high performance liquid chromatography/mass spectrometry shows that a product is formed with a relative molecular mass (Mr) equal to CP15 plus 176. Serotonin, an abundant component of platelet-dense granules, has an Mr of 176, and fibrinogen isolated from COAT-platelets contains covalently linked serotonin. Synthetic bovine serum albumin-(serotonin)6 binds selectively to COAT-platelets and also inhibits the retention of procoagulant proteins on COAT-platelets. These data indicate that COAT-platelets use serotonin conjugation to augment the retention of procoagulant proteins on their cell surface through an as yet unidentified serotonin receptor.
Dale
George L
GL
W. K. Warren Medical Research Institute and Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. george-dale@ouhsc.edu
Friese
Paul
P
Batar
Peter
P
Hamilton
Stephen F
SF
Reed
Guy L
GL
Jackson
Kenneth W
KW
Clemetson
Kenneth J
KJ
Alberio
Lorenzo
L
D000595:Amino Acid Sequence; D000818:Animals; D001710:Biotin / Q000378:metabolism; D001777:Blood Coagulation; D001779:Blood Coagulation Factors; D001792:Blood Platelets / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005165:Factor V / Q000378:metabolism; D005176:Factor XIII / Q000378:metabolism; D005340:Fibrinogen; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D015539:Platelet Activation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D011485:Protein Binding; D012701:Serotonin; D011503:Transglutaminases / Q000378:metabolism
D001779:Blood Coagulation Factors; D010455:Peptides; D019038:Platelet Glycoprotein GPIb-IX Complex; D012701:Serotonin; D001710:Biotin; D005165:Factor V; D005340:Fibrinogen; D005176:Factor XIII; D011503:Transglutaminases