Arf6 plays an early role in platelet activation by collagen and convulxin.

TitleArf6 plays an early role in platelet activation by collagen and convulxin.
Publication TypeJournal Article
Year of Publication2006
JournalBlood
Volume107
Issue8
Pagination3145-52
Date Published2006 Apr 15
ISSN0006-4971
AbstractSmall GTPases play critical roles in hemostasis, though the roster of such molecules in platelets is not complete. In this study, we report the presence of Ras-related GTPases of the ADP-ribosylation factor (Arf) family. Platelets contain Arf1 or 3 and Arf6, with the latter being predominantly membrane associated. Using effector domain pull-down assays, we show, counter to other GTPases, that Arf6-GTP is present in resting platelets and decreases rapidly upon activation with collagen or convulxin. This decrease does not completely rely on secondary agonists (ADP and thromboxane A2) or require integrin signaling. The decrease in free Arf6-GTP temporally precedes activation of Rho family GTPases (RhoA, Cdc42, and Rac1). Using a membrane-permeant, myristoylated peptide, which mimics the N-terminus of Arf6, we show that the Arf6-GTP decrease is essential for collagen- and convulxin-induced aggregation, platelet adherence, and spreading on collagen-coated glass. Treatment with this peptide also affects the activation of Rho family GTPases, but has little effect on RalA and Rap1 or on agonist-induced calcium mobilization. These data show that Arf6 is a key element in activation through GPVI, and is required for activation of the Rho family GTPases and the subsequent cytoskeletal rearrangements needed for full platelet function.
URLhttp://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=16352809
DOI10.1182/blood-2005-09-3563
PubMed Linkhttp://www.ncbi.nlm.nih.gov/pubmed/16352809?dopt=Abstract
Short TitleBlood