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PubMed2003

COAT platelets.

PURPOSE OF REVIEW: COAT platelets are a recently described subpopulation of cells resulting from simultaneous activation with collagen and thrombin. The complete process by which COAT platelets are produced is still not clear, although significant recent progress has been made. RECENT FINDINGS: COAT platelets retain several procoagulant proteins on their surface by a previously unrecognized mechanism involving transglutaminase mediated conjugation of serotonin to released alpha-granule proteins. Fibrinogen and thrombospondin have been found to bind serotonin-conjugated proteins and thereby provide the requisite link for stabilization of serotonin-derivatized, procoagulant proteins on COAT platelets. SUMMARY: Multivalent interactions, resulting from traditional receptor interactions and binding of conjugated serotonin by fibrinogen and thrombospondin, result in exceptionally strong retention of procoagulant alpha-granule proteins on the surface of COAT platelets. The physiologic significance of this new subclass of platelets remains to be determined.

Blood Platelets↗

PubMed2002

Thrombospondin and fibrinogen bind serotonin-derivatized proteins on COAT-platelets.

Activation of platelets with 2 agonists, collagen and thrombin, reveals a subpopulation of cells referred to as COAT-platelets (collagen and thrombin activated). These cells are enriched in several membrane-bound, procoagulant proteins, including fibrinogen, thrombospondin, factor V, von Willebrand factor, and fibronectin. alpha-Granule proteins bound to COAT-platelets are derivatized with serotonin by a transglutaminase-mediated process, and the interaction of conjugated serotonins with unidentified serotonin binding sites on the platelet surface enhances retention of these proteins. We now demonstrate that both thrombospondin and fibrinogen provide the requisite serotonin binding sites. Thrombospondin and fibrinogen were identified using photoreactive cross-linking to an albumin-(serotonin)(6) conjugate during COAT-platelet production. We subsequently verified that biotin-albumin-(serotonin)(6) binds in vitro to thrombospondin, fibrinogen, and fibrinogen fragment D in a saturable manner. These data support a model for COAT-platelets where serotonin-derivatized procoagulant proteins interact with their respective receptors (eg, fibrinogen with glycoprotein IIb/IIIa or factor V with phosphatidylserine) as well as serotonin binding sites on fibrinogen and thrombospondin, resulting in a stable, multivalent complex on the cell surface.

Binding Sites↗