2022
DOI: 10.3390/ijms23073746
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Rac Inhibition Causes Impaired GPVI Signalling in Human Platelets through GPVI Shedding and Reduction in PLCγ2 Phosphorylation

Abstract: Rac1 is a small Rho GTPase that is activated in platelets upon stimulation with various ligands, including collagen and thrombin, which are ligands for the glycoprotein VI (GPVI) receptor and the protease-activated receptors, respectively. Rac1-deficient murine platelets have impaired lamellipodia formation, aggregation, and reduced PLCγ2 activation, but not phosphorylation. The objective of our study is to investigate the role of Rac1 in GPVI-dependent human platelet activation and downstream signalling. Ther… Show more

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Cited by 4 publications
(3 citation statements)
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References 72 publications
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“…The human and murine platelets were lysed at a concentration of 5 × 10 8 /mL in an IP-buffer containing a protease inhibitor cocktail. The platelet lysates were mixed with a loading buffer containing SDS and pre-heated to 95 °C for 5 min before loading in a 10% polyacrylamide gel, and the immunoblotting was performed as previously described [ 46 , 47 ].…”
Section: Methodsmentioning
confidence: 99%
“…The human and murine platelets were lysed at a concentration of 5 × 10 8 /mL in an IP-buffer containing a protease inhibitor cocktail. The platelet lysates were mixed with a loading buffer containing SDS and pre-heated to 95 °C for 5 min before loading in a 10% polyacrylamide gel, and the immunoblotting was performed as previously described [ 46 , 47 ].…”
Section: Methodsmentioning
confidence: 99%
“…Tspan15 can also interact with the Rho GTPase Rac1 [ 11 ], which modulates the GPVI surface expression. Neagoe et al [ 12 ] investigated the role of Rac1 in human platelet activation and downstream signaling using the inhibitor EHT1864. This inhibitor did not affect the collagen-induced clustering of GPVI, but decreased the spreading and aggregation when platelets were stimulated by GPVI agonists.…”
mentioning
confidence: 99%
“…Studies report a difference in (activation-induced) GPVI shedding from the platelet surface, claiming that in mouse platelets GPVI is cleaved by both the ADAM10 and ADAM17 proteases, while in human platelets this job is mainly carried out by ADAM10. 105,106 Second, huGPVI but not mGPVI is able to support the activation and spreading of platelets on immobilized fibrinogen. 107 This may have implications for the precise roles of huGPVI and mGPVI in thrombus formation.…”
Section: Gpvi and Clec-2 Differencesmentioning
confidence: 98%