Rap1b is required for normal platelet function and hemostasis in mice

Magdalena Chrzanowska-Wodnicka, Susan S. Smyth, Simone M. Schoenwaelder, Thomas H. Fischer, Gilbert C. White

Research output: Contribution to journalArticlepeer-review

268 Scopus citations

Abstract

Rap1b, an abundant small GTPase in platelets, becomes rapidly activated upon stimulation with agonists. Though it has been implicated to act downstream from G protein-coupled receptors (GPCRs) and upstream of integrin αIIbβ3, the precise role of Rap1b in platelet function has been elusive. Here we report the generation of a murine rap1b knockout and show that Rap1b deficiency results in a bleeding defect due to defective platelet function. Aggregation of Rap1b-null platelets is reduced in response to stimulation with both GPCR-linked and GPCR-independent agonists. Underlying the defective Rap1b-null platelet function is decreased activation of integrin αIIbβ3 in response to stimulation with agonists and signaling downstream from the integrin α IIbβ3. In vivo, Rap1b-null mice are protected from arterial thrombosis. These data provide genetic evidence that Rap1b is involved in a common pathway of integrin activation, is required for normal hemostasis in vivo, and may be a clinically relevant antithrombotic therapy target.

Original languageEnglish
Pages (from-to)680-687
Number of pages8
JournalJournal of Clinical Investigation
Volume115
Issue number3
DOIs
StatePublished - Mar 2005

ASJC Scopus subject areas

  • General Medicine

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