Adenine dinucleotide second messengers and T-lymphocyte calcium signaling

• Main Authors: Insa MA Ernst, Ralf eFliegert, Andreas H Guse
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2013-08-01
• Series: Frontiers in Immunology
• Subjects: Calcium Signaling; calcium release; TRPM2 cation channels; T-lymphocyte; Nicotinic acid adenine dinucleotide phosphate (NAADP); cyclic ADP-ribose (cADPR)
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00259/full

Calcium signaling is a universal signal transduction mechanism in animal and plant cells. In mammalian T-lymphocytes calcium signaling is essential for activation and re-activation and thus important for a functional immune response. Since many years it has been known that both calcium release from intracellular stores and calcium entry via plasma membrane calcium channels are involved in shaping spatio-temporal calcium signals. Second messengers derived from the adenine dinucleotides NAD and NADP have been implicated in T cell calcium signaling. Nicotinic acid adenine dinucleotide phosphate (NAADP) acts as a very early second messenger upon T cell receptor/CD3 engagement, while cyclic ADP-ribose (cADPR) mainly is involved in sustained partial depletion of the endoplasmic reticulum by stimulating calcium release via ryanodine receptors. Finally, adenosine diphosphoribose (ADPR) a breakdown product of both NAD and cADPR activates a plasma membrane cation channel termed TRPM2 thereby facilitating calcium (and sodium) entry into T cells.Receptor-mediated formation, metabolism and mode of action of these novel second messengers in T-lymphocytes will be reviewed.