Rho GTPase regulation of reactive oxygen species generation and signalling in platelet function and disease

Anh T.P. Ngo, Ivan Parra-Izquierdo, Joseph E. Aslan, Owen J.T. McCarty

Research output: Contribution to journalReview articlepeer-review

Abstract

Platelets are master regulators and effectors of haemostasis with increasingly recognized functions as mediators of inflammation and immune responses. The Rho family of GTPase members Rac1, Cdc42 and RhoA are known to be major components of the intracellular signalling network critical to platelet shape change and morphological dynamics, thus playing a major role in platelet spreading, secretion and thrombus formation. Initially linked to the regulation of actomyosin contraction and lamellipodia formation, recent reports have uncovered non-canonical functions of platelet RhoGTPases in the regulation of reactive oxygen species (ROS), where intrinsically generated ROS modulate platelet function and contribute to thrombus formation. Platelet RhoGTPases orchestrate oxidative processes and cytoskeletal rearrangement in an interconnected manner to regulate intracellular signalling networks underlying platelet activity and thrombus formation. Herein we review our current knowledge of the regulation of platelet ROS generation by RhoGTPases and their relationship with platelet cytoskeletal reorganization, activation and function.

Original languageEnglish (US)
Pages (from-to)440-457
Number of pages18
JournalSmall GTPases
Volume12
Issue number5-6
DOIs
StatePublished - 2021

Keywords

  • Rho GTPases
  • hemostasis
  • oxidative stress
  • platelets
  • thrombosis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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