title: Adenine Dinucleotide Second Messengers and T-lymphocyte Calcium Signaling.
abstract: 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) is mainly 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.
authors.affiliation: The Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Insa M A
authors.initials: IM
authors.lastname: Ernst
authors.forename: Ralf
authors.initials: R
authors.lastname: Fliegert
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Guse
keywords: T-lymphocyte; TRPM2 cation channels; adenosine diphosphoribose; calcium entry; calcium release; calcium signaling; cyclic ADP-ribose; nicotinic acid adenine dinucleotide phosphate