| First Author | Gu F | Year | 2021 |
| Journal | Sci Signal | Volume | 14 |
| Issue | 709 | Pages | eabe3800 |
| PubMed ID | 34784249 | Mgi Jnum | J:337880 |
| Mgi Id | MGI:7506756 | Doi | 10.1126/scisignal.abe3800 |
| Citation | Gu F, et al. (2021) Dual NADPH oxidases DUOX1 and DUOX2 synthesize NAADP and are necessary for Ca(2+) signaling during T cell activation. Sci Signal 14(709):eabe3800 |
| abstractText | The formation of Ca(2+) 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 Ca(2+) signaling were decreased in mouse T cells with double knockout of Duoxa1 and Duoxa2 but not with knockout of Nox1 or Nox2. Ca(2+) 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 Ca(2+) 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. |
