Related Experiment Video

Updated: Sep 27, 2025

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry
04:32

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry

Published on: June 5, 2019

7.8K

Rac Inhibition Causes Impaired GPVI Signalling in Human Platelets through GPVI Shedding and Reduction in PLCγ2

Raluca A I Neagoe1,2, Elizabeth E Gardiner3, David Stegner2

  • 1Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.

International Journal of Molecular Sciences
|April 12, 2022
PubMed

Insights

Rac1 protein is crucial for human and mouse platelet activation via GPVI signaling. However, Rac1 inhibition impairs human platelet aggregation and spreading, unlike in mice, suggesting species-specific roles.

Area of Science:

  • Platelet biology
  • Cell signaling
  • Rho GTPases

Background:

  • Rac1, a Rho GTPase, is activated in platelets by ligands like collagen and thrombin.
  • Rac1 deficiency in mice impairs platelet functions such as lamellipodia formation and aggregation.

Purpose of the Study:

  • To investigate the role of Rac1 in human platelet activation and signaling pathways downstream of the glycoprotein VI (GPVI) receptor.

Main Methods:

  • Human platelets were stimulated with GPVI agonists (collagen, collagen-related peptide).
  • The specific Rac1 inhibitor EHT1864 was used to assess Rac1's role.
  • Platelet activation, aggregation, spreading, protein phosphorylation, GPVI clustering, and shedding were analyzed.

Main Results:

  • Rac1 inhibition did not affect GPVI clustering but reduced human platelet spreading and aggregation.
  • Unlike in murine platelets, Rac1 inhibition enhanced GPVI shedding and reduced PLCγ2 phosphorylation in human platelets.
  • Rac1 activity is essential for GPVI-dependent platelet activation in both species.

Conclusions:

  • Rac1 plays a vital role in human and murine platelet activation mediated by GPVI ligands.
  • The functional mechanism of Rac1 in platelet activation differs between human and mouse platelets.
Keywords:
EHT1864GPVI sheddingRac1glycoprotein VIphospholipase C gamma 2platelets

More Related Videos

Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation04:37

Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation

Published on: May 23, 2025

670
Turbidimetry on Human Washed Platelets: The Effect of the Pannexin1-inhibitor Brilliant Blue FCF on Collagen-induced Aggregation09:13

Turbidimetry on Human Washed Platelets: The Effect of the Pannexin1-inhibitor Brilliant Blue FCF on Collagen-induced Aggregation

Published on: April 6, 2017

12.1K

Related Concept Videos

Formation of the Platelet Plug01:22

Formation of the Platelet Plug

The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
7.3K
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.7K
Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors01:20

Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors

Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
662
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.0K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.9K
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
4.9K