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José Manuel Cancela"Le NAADP, un messager libérant du calcium: un nouvel acteur dans le système nerveux ? "

Abstract :

Calcium is one of the most versatile and important intracellular messengers in living cells and organisms. Ca2+ is involved in the control of numerous biological processes. Such as for egg fertilization, synaptic plasticity, muscle cell contraction, gene expression, enzyme secretion and cell proliferation. Ca2+ signals are not all-or-none events; they vary greatly in amplitude, duration and localization. How such specific Ca2+ signals, and thereby specific physiological responses, are generated is an intense area of research. Within cell, Ca2+ signals depend upon Ca2+ entry and/or Ca2+ release from internal Ca2+ stores. The control of Ca2+-store mobilization is ensured by a family of messengers comprising inositol 1,4,5 trisphosphate, cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP). NAADP is the most potent Ca2+ mobilizing intracellular messenger and linked to a variety of stimuli and cell surface receptors. We have provided the first evidence of a messenger role for NAADP using the prototypical pancreatic acinar cells[1]. In these cells, we have shown that the hormone cholecystokinin (CCK) stimulates NAADP production evoking Ca2+ signals by discharging acidic Ca2+stores and leading to granule and lysosome secretion[2]. From our and collaborator’s recent works, new concepts have emerged where activation of the cells by outside stimuli, acting at the plasma membrane, results in the synthesis of multiple Ca2+ releasing messengers which may interact and shape complex Ca2+ signals in the cytosol as well as in the nucleus[3, 4]. This contribution will cover the most recent advances on NAADP signalling with some emphasis on neurons.

Selected publications

Cancela, J.M., Churchill, G.C., and Galione, A. (1999). Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cells. Nature 398, 74-76.
Menteyne, A., Burdakov, A., Charpentier, G., Petersen, O.H., and Cancela, J.M. (2006). Generation of specific Ca(2+) signals from Ca(2+) stores and endocytosis by differential coupling to messengers. Curr Biol 16, 1931-1937.
Yamasaki, M., Thomas, J.M., Churchill, G.C., Garnham, C., Lewis, A.M., Cancela, J.M., Patel, S., and Galione, A. (2005). Role of NAADP and cADPR in the induction and maintenance of agonist-evoked Ca2+ spiking in mouse pancreatic acinar cells. Curr Biol 15, 874-878.

Bezin, S., Charpentier, G., Lee, H.C., Baux, G., Fossier, P., and Cancela, J.M. (2008). Regulation of nuclear Ca2+ signaling by translocation of the Ca2+ messenger synthesizing enzyme ADP-ribosyl cyclase during neuronal depolarization. The Journal of biological chemistry 283, 27859-27870.