CD38: A NAADP degrading enzyme

• Published in: FEBS letters 2011-11, Vol.585 (22), p.3544-3548
• Main Authors: Schmid, Frederike, Bruhn, Sören, Weber, Karin, Mittrücker, Hans-Willi, Guse, Andreas H.
• Format: Article
• Language: English
• Subjects: 2-phospho adenosine diphosphoribose; Adenosine Diphosphate Ribose - metabolism; adenosine diphosphoribose; ADP-ribosyl Cyclase 1 - genetics; ADP-ribosyl Cyclase 1 - metabolism; ADPR; ADPRP; Animals; cADPR; Calcium - metabolism; Calcium signalling; CD38; cyclic adenosine diphosphoribose; FACS; fluorescence activated cell sorting; Gene Silencing; Humans; Jurkat Cells; Jurkat T lymphocyte; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Mice, Knockout; NAADP; NADP - analogs & derivatives; NADP - metabolism; nicotinic acid adenine dinucleotide phosphate; Spleen - metabolism; T cell receptor; TCR; Thymus Gland - metabolism
• ISSN: 0014-5793; 1873-3468; 1873-3468
• DOI: 10.1016/j.febslet.2011.10.017

► We studied the role of CD38 in formation of the second messenger NAADP. ► We used gene silencing and CD38 KO mice to show a lack of inhibition of NAADP synthesis. ► We conclude that CD38 appears to be a NAADP degrading enzyme in intact cells. The role of the multifunctional enzyme CD38 in formation of the Ca 2+-mobilizing second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) was investigated. Gene silencing of CD38 did neither inhibit NAADP synthesis in intact Jurkat T cells nor in thymus or spleen obtained from CD38 knock out mice. In vitro, both NAADP formation by base-exchange and degradation to 2-phospho adenosine diphosphoribose were efficiently decreased. Thus in vivo CD38 appears to be a NAADP degrading rather than a NAADP forming enzyme, perhaps avoiding desensitizing NAADP levels in intact cells.