Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface

George L. Dale, Paul Friese, Peter Batar, Stephen F. Hamilton, Guy Reed, Kenneth W. Jackson, Kenneth J. Clemetson, Lorenzo Alberio

Research output: Contribution to journalLetter

225 Citations (Scopus)

Abstract

Activated platelets bind numerous adhesive and procoagulant proteins by receptor-mediated processes1. 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 α-granule factor V only on a subpopulation of cells2. Here we show that these cells, referred to as 'COAT-platelets', bind additional α-granule proteins, including fibrinogen, von Willebrand factor, thrombospondin, fibronectin and α2-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 granules3, 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.

Original languageEnglish (US)
Pages (from-to)175-179
Number of pages5
JournalNature
Volume415
Issue number6868
DOIs
StatePublished - Jan 1 2002

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Serotonin
Membrane Proteins
Blood Platelets
Transglutaminases
Proteins
Fibrinogen
Antifibrinolytic Agents
Factor V
Serotonin Receptors
von Willebrand Factor
Bovine Serum Albumin
Fibronectins
Thrombin
Adhesives
Mass Spectrometry
Collagen
High Pressure Liquid Chromatography

All Science Journal Classification (ASJC) codes

  • General

Cite this

Dale, G. L., Friese, P., Batar, P., Hamilton, S. F., Reed, G., Jackson, K. W., ... Alberio, L. (2002). Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface. Nature, 415(6868), 175-179. https://doi.org/10.1038/415175a

Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface. / Dale, George L.; Friese, Paul; Batar, Peter; Hamilton, Stephen F.; Reed, Guy; Jackson, Kenneth W.; Clemetson, Kenneth J.; Alberio, Lorenzo.

In: Nature, Vol. 415, No. 6868, 01.01.2002, p. 175-179.

Research output: Contribution to journalLetter

Dale, GL, Friese, P, Batar, P, Hamilton, SF, Reed, G, Jackson, KW, Clemetson, KJ & Alberio, L 2002, 'Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface', Nature, vol. 415, no. 6868, pp. 175-179. https://doi.org/10.1038/415175a
Dale GL, Friese P, Batar P, Hamilton SF, Reed G, Jackson KW et al. Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface. Nature. 2002 Jan 1;415(6868):175-179. https://doi.org/10.1038/415175a
Dale, George L. ; Friese, Paul ; Batar, Peter ; Hamilton, Stephen F. ; Reed, Guy ; Jackson, Kenneth W. ; Clemetson, Kenneth J. ; Alberio, Lorenzo. / Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface. In: Nature. 2002 ; Vol. 415, No. 6868. pp. 175-179.
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