en
Scientific article
English

Dual NADPH oxidases DUOX1 and DUOX2 synthesize NAADP and are necessary for Ca2+ signaling during T cell activation

Published inScience signaling, vol. 14, no. 709, eabe3800
Publication date2021-11-16
First online date2021-11-16
Abstract

The formation of Ca2+ microdomains during T cell activation is initiated by the production of nicotinic acid adenine dinucleotide phosphate (NAADP) from its reduced form NAADPH. The reverse reaction—NAADP to NAADPH—is catalyzed by glucose 6-phosphate dehydrogenase (G6PD). Here, we identified NADPH oxidases NOX and DUOX as NAADP-forming enzymes that convert NAADPH to NAADP under physiological conditions in vitro. T cells express NOX1, NOX2, and, to a minor extent, DUOX1 and DUOX2. Local and global Ca2+ signaling were decreased in mouse T cells with double knockout of Duoxa1 and Duoxa2 but not with knockout of Nox1 or Nox2. Ca2+ microdomains in the first 15 s upon T cell activation were significantly decreased in Duox2−/− but not in Duox1−/− T cells, whereas both DUOX1 and DUOX2 were required for global Ca2+ signaling between 4 and 12 min after stimulation. Our findings suggest that a DUOX2- and G6PD-catalyzed redox cycle rapidly produces and degrades NAADP through NAADPH as an inactive intermediate.

eng
Keywords
  • Animals
  • Calcium Signaling
  • Dual Oxidases / genetics
  • HEK293 Cells
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation
  • Mice, Knockout
  • NADP / analogs & derivatives
  • NADP / biosynthesis
  • NADPH Oxidases / genetics
  • T-Lymphocytes / enzymology
Citation (ISO format)
GU, Feng et al. Dual NADPH oxidases DUOX1 and DUOX2 synthesize NAADP and are necessary for Ca2+ signaling during T cell activation. In: Science signaling, 2021, vol. 14, n° 709, p. eabe3800. doi: 10.1126/scisignal.abe3800
Main files (1)
Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1945-0877
115views
0downloads

Technical informations

Creation03/02/2022 9:37:00 AM
First validation03/02/2022 9:37:00 AM
Update time03/16/2023 2:47:14 AM
Status update03/16/2023 2:47:11 AM
Last indexation05/06/2024 10:13:19 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack