Serotonylation of Small GTPases Is a Signal Transduction Pathway that Triggers Platelet α-Granule Release

@article{Walther2003SerotonylationOS,
  title={Serotonylation of Small GTPases Is a Signal Transduction Pathway that Triggers Platelet $\alpha$-Granule Release},
  author={Diego J. Walther and J. Peter and Sandra Winter and Markus H{\"o}ltje and Nils Paulmann and Maik Grohmann and Jakob Vowinckel and Victor Alamo-Bethencourt and Claudia S Wilhelm and Gudrun Ahnert-Hilger and Michael Bader},
  journal={Cell},
  year={2003},
  volume={115},
  pages={851-862}
}

Figures from this paper

Platelet Kainate Receptor Signaling Promotes Thrombosis by Stimulating Cyclooxygenase Activation
TLDR
The data demonstrate that glutamate regulation of platelet activation is in part cyclooxygenase-dependent and suggest that the KAR is a novel antithrombotic target.
Serotonylation: Serotonin Signaling and Epigenetics
  • M. Bader
  • Biology, Chemistry
    Front. Mol. Neurosci.
  • 2019
Serotonylation, the covalent linkage of serotonin to proteins has been discovered more than 60 years ago but only recently the mechanisms and first functions have been elucidated. It has been found
Partially Defective Store Operated Calcium Entry and Hem(ITAM) Signaling in Platelets of Serotonin Transporter Deficient Mice
TLDR
Although secreted platelet 5-HT does not appear to play a crucial role in the development of reperfusion injury after stroke, it is essential to amplify the second phase of platelet activation through SOCE and plays an important role in thrombus stabilization.
Role of a serotonin precursor in development of gut microvilli.
TLDR
It is shown that endogenous and exogenous 5-HTP but not serotonin induced the development of microvilli in the gut villi epithelium and inhibition of ERK activity promoted theDevelopment of microVilli inThe gut and ameliorated phagocytosis by macrophages.
Autocrine and paracrine regulatory functions of platelet serotonin
TLDR
The current state of basic biological research regarding the hemostatic and non-hemostatic functions of platelet-derived 5-HT in normal and disease conditions are highlighted and the physiological consequences of targeting platelet 5- HT functions in thrombosis, stroke, inflammation and cancer to overcome common health problems are described.
Serotonin—more than a neurotransmitter: transglutaminase-mediated serotonylation of C6 glioma cells and fibronectin
Down-regulation of the serotonin transporter in hyperreactive platelets counteracts the pro-thrombotic effect of serotonin.
Development of antithrombotic miniribozymes that target peripheral tryptophan hydroxylase
TLDR
This active tRNA–miniribozyme chimera is capable of selectively cleaving native Tph1 mRNA in vivo, with concomitant downregulation of the serotonin biosynthesis, and may provide a novel and effective form of gene therapy that may be applicable to a variety of thrombotic diseases.
...
...

References

SHOWING 1-10 OF 83 REFERENCES
Platelet-vessel wall interactions in hemostasis: Implication of 5-hydroxytryptamine
TLDR
The present study shows the interplay between the platelet-derived mediators 5-HT and TXA2 at the level of the Platelet or the blood vessel to be of major importance in the platelets-vessel wall interactions during hemostasis.
Defective platelet activation in G alpha(q)-deficient mice.
TLDR
It is shown that platelets from mice deficient in the alpha-subunit of the heterotrimeric guanine-nucleotide-binding protein Gq are unresponsive to a variety of physiological platelet activators and that G alpha(q) may be a new target for drugs designed to block the activation of platelets.
Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface
TLDR
Data indicate that COAT-platelets use serotonin conjugation to augment the retention of procoagulant proteins on their cell surface through an as yet unidentified serotonin receptor.
Activation of the small GTPases, rac and cdc42, after ligation of the platelet PAR-1 receptor.
TLDR
Differences in subcellular distribution and previous evidence showing quantitatively divergent effects of rac and cdc42 on actin nucleation in permeabilized platelets indicate different signaling roles for these GTPases.
Adenosine nucleotides and serotonin stimulate von Willebrand factor release from cultured human endothelial cells.
TLDR
The effects of the platelet secretagogues ADP, AMP, ATP and serotonin on the release of vWf from ECs were examined and enhanced release in all cases and depended on the agonist and its concentration.
Small GTPase Rho regulates thrombin-induced platelet aggregation.
TLDR
An assay system is established using platelets permeabilized with streptolysin-O to analyze mechanism of the thrombin-induced aggregation of platelets, focusing upon a controversial issue in the field whether small GTPase Rho regulates the aggregation.
Small GTPase Rab4 Regulates Ca2+-induced α-Granule Secretion in Platelets*
TLDR
In platelets, the regulatory mechanisms governing α- and dense-core granule secretions are distinct, and Rab4 is an essential regulator of the Ca2+-induced exocytosis of α-granules.
Thrombospondin and fibrinogen bind serotonin-derivatized proteins on COAT-platelets.
TLDR
Data support a model for COAT-platelets where serotonin-derivatized procoagulant proteins interact with their respective receptors as well as serotonin binding sites on fibrinogen and thrombospondin, resulting in a stable, multivalent complex on the cell surface.
...
...