title: Procoagulant platelets form an α-granule protein-covered "cap" on their surface that promotes their attachment to aggregates.
abstract: Strongly activated "coated" platelets are characterized by increased phosphatidylserine (PS) surface expression, α-granule protein retention, and lack of active integrin αIIbβ3. To study how they are incorporated into thrombi despite a lack of free activated integrin, we investigated the structure, function, and formation of the α-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 αIIbβ3. 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.
authors.affiliation: From the Center for Theoretical Problems of Physicochemical Pharmacology, 119991 Moscow, Russia.
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Abaeva
authors.forename: Matthias
authors.initials: M
authors.lastname: Canault
authors.forename: Yana N
authors.initials: YN
authors.lastname: Kotova
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Obydennyy
authors.forename: Alena O
authors.initials: AO
authors.lastname: Yakimenko
authors.forename: Nadezhda A
authors.initials: NA
authors.lastname: Podoplelova
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Kolyadko
authors.forename: Herve
authors.initials: H
authors.lastname: Chambost
authors.forename: Aleksei V
authors.initials: AV
authors.lastname: Mazurov
authors.forename: Fazoil I
authors.initials: FI
authors.lastname: Ataullakhanov
authors.forename: Alan T
authors.initials: AT
authors.lastname: Nurden
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Panteleev
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000494:pharmacology; D010718:Phosphatidylserines / Q000378:metabolism; D010974:Platelet Aggregation; D058105:Polymerization / Q000187:drug effects; D013915:Thrombasthenia / Q000097:blood / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism; D019699:Thrombospondins / Q000378:metabolism*; D011503:Transglutaminases / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D010718:Phosphatidylserines; D019699:Thrombospondins; C034585:glycyl-prolyl-arginyl-proline; D005337:Fibrin; D005340:Fibrinogen; D011503:Transglutaminases
keywords: Fibrinogen; Integrin αIIbβ3; Phosphatidylserine; Platelet Aggregation; Platelets; Thrombospondin; Transglutaminases