Regulation of nuclear Ca2+ signaling by translocation of the Ca2+ messenger synthesizing enzyme ADP-ribosyl cyclase during neuronal depolarization.
In neurons, voltage-gated Ca(2+) channels and nuclear Ca(2+) signaling play important roles, such as in the regulation of gene expression. However, the link between electrical activity and biochemical cascade activation involved in the generation of the nuclear Ca(2+) signaling is poorly understood. Here we show that depolarization of Aplysia neurons induces the translocation of ADP-ribosyl cyclase, a Ca(2+) messenger synthesizing enzyme, from the cytosol into the nucleus. The translocation is dependent on Ca(2+) influx mainly through the voltage-dependent L-type Ca(2+) channels. We report also that specific nucleoplasmic Ca(2+) signals can be induced by three different calcium messengers, cyclic ADP-ribose, nicotinic acid adenine dinucleotide phosphate (NAADP), both produced by the ADP-ribosyl cyclase, and inositol 1,4,5-trisphosphate (IP(3)). Moreover, our pharmacological data show that NAADP acts on its own receptor, which cooperates with the IP(3) and the ryanodine receptors to generate nucleoplasmic Ca(2+) oscillations. We propose a new model where voltage-dependent L-type Ca(2+) channel-induced nuclear translocation of the cytosolic cyclase is a crucial step in the fine tuning of nuclear Ca(2+) signals in neurons.
Bezin
Stéphanie
S
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, UPR 9040, 1, Avenue de la Terrasse, 91198 Gif-Sur-Yvette Cedex, France.
Charpentier
Gilles
G
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, UPR 9040, 1, Avenue de la Terrasse, 91198 Gif-Sur-Yvette Cedex, France; Université Bordeaux 1 Laboratoire DMPFCS, IECB, 2, Rue Robert Escarpit, 33607 Pessac, France.
Lee
Hon Cheung
HC
Department of Physiology, University of Hong Kong, 4/F Lab Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong.
Baux
Gérard
G
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, UPR 9040, 1, Avenue de la Terrasse, 91198 Gif-Sur-Yvette Cedex, France.
Fossier
Philippe
P
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, UPR 9040, 1, Avenue de la Terrasse, 91198 Gif-Sur-Yvette Cedex, France.
Cancela
José-Manuel
JM
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, UPR 9040, 1, Avenue de la Terrasse, 91198 Gif-Sur-Yvette Cedex, France. Electronic address: jose.cancela@nbcm.cnrs-gif.fr.
D036541:ADP-ribosyl Cyclase / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D001048:Aplysia / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002467:Cell Nucleus / Q000201:enzymology*; D036563:Cyclic ADP-Ribose / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D009249:NADP / Q000031:analogs & derivatives / Q000378:metabolism; D009474:Neurons / Q000201:enzymology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D036563:Cyclic ADP-Ribose; D009249:NADP; C024376:NAADP; D015544:Inositol 1,4,5-Trisphosphate; D036541:ADP-ribosyl Cyclase; D002118:Calcium