Glycoprotein VI agonists have distinct dependences on the lipid raft environment.
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.
Quinter
P G
PG
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Dangelmaier
C A
CA
Quinton
T M
TM
Kunapuli
S P
SP
Daniel
J L
JL
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D001792:Blood Platelets; D003094:Collagen / Q000494:pharmacology; D025461:Feedback, Physiological; D006801:Humans; D021962:Membrane Microdomains / Q000502:physiology*; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000819:agonists*; D015398:Signal Transduction
D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D000244:Adenosine Diphosphate; D003094:Collagen