Role of the Rho GTPase Rac in the activation of the phagocyte NADPH oxidase: Outsourcing a key task

Research output: Contribution to journalReview articlepeer-review

Abstract

The superoxide-generating NADPH oxidase of phagocytes consists of the membrane-associated cytochrome b558 (a heterodimer of Nox2 and p22phox) and 4 cytosolic components: p47phox, p67phox, p40phox, and the small GTPase, Rac, in complex with RhoGDI. Superoxide is produced by the NADPH-driven reduction of molecular oxygen, via a redox gradient located in Nox2. Electron flow in Nox2 is initiated by interaction with cytosolic components, which translocate to the membrane, p67phox playing the central role.the participation of Rac is expressed in the following sequence: (1) Translocation of the RacGDP-RhoGDI complex to the membrane; (2) Dissociation of RacGDP from RhoGDI; (3) GDP to GTP exchange on Rac, mediated by a guanine nucleotide exchange factor; (4) Binding of RacGTP to p67phox; (5) Induction of a conformational change in p67phox, promoting interaction with Nox2.the particular involvement of Rac in NADPH oxidase assembly serves as a paradigm for signaling by Rho GTPases, in general.

Original languageEnglish
Article numbere27952
JournalSmall GTPases
Volume5
Issue numberMAR
DOIs
StatePublished - 2014

Keywords

  • Cell-free system
  • GEF
  • NADPH oxidase
  • Rac1
  • Rac2
  • Rho GTPases
  • RhoGDI
  • Superoxide

Fingerprint

Dive into the research topics of 'Role of the Rho GTPase Rac in the activation of the phagocyte NADPH oxidase: Outsourcing a key task'. Together they form a unique fingerprint.

Cite this