Article Dans Une Revue Journal of Biological Chemistry Année : 2013

Procoagulant Platelets Form an -Granule Protein-covered "Cap" on Their Surface That Promotes Their Attachment to Aggregates

Résumé

Strongly activated "coated" platelets are characterized by increased phosphatidylserine (PS) surface expression, alpha-granule protein retention, and lack of active integrin alpha(IIb)beta(3). To study how they are incorporated into thrombi despite a lack of free activated integrin, we investigated the structure, function, and formation of the alpha-granule protein "coat." Confocal microscopy revealed that fibrin(ogen) and thrombospondin colocalized as "cap," a single patch on the PS-positive platelet surface. In aggregates, the cap was located at the point of attachment of the PS-positive platelets. Without fibrin(ogen) retention, their ability to be incorporated in aggregates was drastically reduced. The surface fibrin(ogen) was strongly decreased in the presence of a fibrin polymerization inhibitor GPRP and also in platelets from a patient with dysfibrinogenemia and a fibrinogen polymerization defect. In contrast, a fibrinogen-clotting protease ancistron increased the amount of fibrin(ogen) and thrombospondin on the surface of the PS-positive platelets stimulated with collagen-related peptide. Transglutaminases are also involved in fibrin( ogen) retention. However, platelets from patients with factor XIII deficiency had normal retention, and a pan-transglutaminase inhibitor T101 had only a modest inhibitory effect. Fibrin( ogen) retention was normal in Bernard-Soulier syndrome and kindlin-3 deficiency, but not in Glanzmann thrombasthenia lacking the platelet pool of fibrinogen and alpha(IIb)beta(3). These data show that the fibrin(ogen)-covered cap, predominantly formed as a result of fibrin polymerization, is a critical mechanism that allows coated (or rather "capped") platelets to become incorporated into thrombi despite their lack of active integrins.

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hal-01478374 , version 1 (28-05-2020)

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A. A. Abaeva, Matthias Canault, Y. N. Kotova, S. I. Obydennyy, A. O. Yakimenko, et al.. Procoagulant Platelets Form an -Granule Protein-covered "Cap" on Their Surface That Promotes Their Attachment to Aggregates. Journal of Biological Chemistry, 2013, 288 (41), pp.29621 - 29632. ⟨10.1074/jbc.M113.474163⟩. ⟨hal-01478374⟩
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