ArticlePflugers Archiv : European journal of physiology2009
Rac1 is essential for phospholipase C-gamma2 activation in platelets.
Article in Pflugers Archiv : European journal of physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 112 citations in OpenAlex.
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- Roles of G proteins and their GTPase-activating proteins in platelets.Bioscience reports · 2024Review
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- Rho GTPase Signaling in Platelet Regulation and Implication for Antiplatelet Therapies.International journal of molecular sciences · 2023Review
- Loss of zinc transporters ZIP1 and ZIP3 augments platelet reactivity in response to thrombin and accelerates thrombus formationFrontiers in immunology · 2023Article
- Impaired microtubule dynamics contribute to microthrombocytopenia in RhoB-deficient mice.Blood advances · 2022Article
- Rac Inhibition Causes Impaired GPVI Signalling in Human Platelets through GPVI Shedding and Reduction in PLCγ2 Phosphorylation.International journal of molecular sciences · 2022Article
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- The brain-derived neurotrophic factor prompts platelet aggregation and secretion.Blood advances · 2021Article
- Novel computational analysis of large transcriptome datasets identifies sets of genes distinguishing chronic obstructive pulmonary disease from healthy lung samples.Scientific reports · 2021Article
- DLDTI: a learning-based framework for drug-target interaction identification using neural networks and network representation.Journal of translational medicine · 2020Article
- Characterisation of the Ral GTPase inhibitor RBC8 in human and mouse platelets.Cellular signalling · 2019Article
- Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting.Journal of hematology & oncology · 2019Review
- Article
- Comparative Analysis of Microfluidics Thrombus Formation in Multiple Genetically Modified Mice: Link to Thrombosis and Hemostasis.Frontiers in cardiovascular medicine · 2019Article
- Reversal of stress fibre formation by Nitric Oxide mediated RhoA inhibition leads to reduction in the height of preformed thrombi.Scientific reports · 2018Article
- Integrin αBlood · 2017Review
- Deletion of the Arp2/3 complex in megakaryocytes leads to microthrombocytopenia in mice.Blood advances · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Platelet activation at sites of vascular injury is triggered through different signaling pathways leading to activation of phospholipase (PL) Cbeta or PLCgamma2. Active PLCs trigger Ca(2+) mobilization and entry, which is a prerequisite for adhesion, secretion, and thrombus formation. PLCbeta isoenzymes are activated downstream of G protein-coupled receptors (GPCRs), whereas PLCgamma2 is activated downstream of immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors, such as the major platelet collagen receptor glycoprotein (GP) VI or CLEC-2. The mechanisms underlying PLC regulation are not fully understood. An involvement of small GTPases of the Rho family (Rho, Rac, Cdc42) in PLC activation has been proposed but this has not been investigated in platelets. We here show that murine platelets lacking Rac1 display severely impaired GPVI- or CLEC-2-dependent activation and aggregation. This defect was associated with impaired production of inositol 1,4,5-trisphosphate (IP(3)) and intracellular calcium mobilization suggesting inappropriate activation of PLCgamma2 despite normal tyrosine phosphorylation of the enzyme. Rac1 ( -/- ) platelets displayed defective thrombus formation on collagen under flow conditions which could be fully restored by co-infusion of ADP and the TxA(2) analog U46619, indicating that impaired GPVI-, but not G-protein signaling, was responsible for the observed defect. In line with this, Rac1 ( -/- ) mice were protected in two collagen-dependent arterial thrombosis models. Together, these results demonstrate that Rac1 is essential for ITAM-dependent PLCgamma2 activation in platelets and that this is critical for thrombus formation in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.