Dynamic tyrosine kinase-regulated signaling and actin polymerisation mediate aggregate stability under shear.

Jocelyn Auger, Steve Watson

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

OBJECTIVE: Aggregate formation on collagen at arteriolar rates of shear is mediated by coordinated signaling between tyrosine kinase-linked and G protein-coupled receptors. We have investigated the role of these receptors and the actin cytoskeleton in maintaining aggregate stability under shear. METHODS AND RESULTS: Platelet aggregates are rapidly formed when blood is flowed over collagen at 1000 s(-1) and remain stable over 20 minutes. A novel fibrin-independent mechanism of retraction against the direction of flow occurs at the aggregate front and recruits platelets into the main aggregate. Stable aggregates are not observed in the presence of cytochalasin D, which blocks de novo actin polymerization. When exposed to the Src family kinase inhibitor, PD0173952, preformed aggregates spread in the direction of flow and rounded platelets appear within the aggregate body and are lost in the direction of flow. A similar set of observations is observed in the presence of latrunculin A, which disrupts preexisting actin filaments, but not in the combined presence of inhibitors of ADP and thromboxane A(2) formation. CONCLUSIONS: Maintenance of stable aggregates at high shear is a dynamic process mediated by Src kinases and actin polymerization. These signals maintain aggregates in a compact structure and prevent continuous streaming of platelets.
Original languageEnglish
Pages (from-to)1499-504
Number of pages6
JournalArteriosclerosis Thrombosis and Vascular Biology
Volume28
Issue number8
DOIs
Publication statusPublished - 1 Aug 2008

Keywords

  • cytoskeleton
  • collagen
  • platelet aggregation
  • shear
  • Src kinase

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