Journal
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 5, Issue 2, Pages 362-368Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1538-7836.2007.02309.x
Keywords
calcium mobilization; glycoprotein VI; lipid rafts; platelets
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Funding
- NHLBI NIH HHS [HL 80444, HL60683] Funding Source: Medline
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Background: It has been reported that the association of glycoprotein VI (GPVI) with lipid rafts regulates GPVI signaling in platelets. Objective: Secreted adenosine 5'-diphosphate (ADP) potentiates GPVI-induced platelet aggregation at particular agonist concentrations. We have investigated whether the decrease in GPVI signaling, previously reported in platelets with disrupted rafts, is a result of the loss of agonist potentiation by ADP. Methods: We disrupted platelet lipid rafts with methyl-beta-cyclodextrin and measured signaling events downstream of GPVI activation. Results: Lipid raft disruption decreases aggregation induced by low concentrations of convulxin, but this decrease is almost eliminated in the presence of ADP antagonists. Signaling indicators, such as protein phosphorylation and calcium mobilization, were not affected by raft disruption in collagen or convulxin stimulated platelets. Interestingly, however, raft disruption directly reduced GPVI signaling induced by collagen-related peptide. Conclusions: Lipid rafts do not directly contribute to signaling by the physiologic agonist collagen. The effects of disruption of lipid rafts in in vitro assays can be attributed to inhibition of ADP feedback that potentiates GPVI signaling.
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