Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text PDF (Full Text) Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bruzzone, S. Articles by Guse, A. H. Search for Related Content PubMed PubMed Citation Articles by Bruzzone, S. Articles by Guse, A. H. Social Bookmarking                      What's this?

¹ Department of Experimental Medicine, Section of Biochemistry
² Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy
³ University Hospital Hamburg-Eppendorf, Centre for Experimental Medicine, Institute of Biochemistry and Molecular Biology I: Cellular Signal Transduction, 20246 Hamburg, Germany

Address correspondence to Andreas Guse, University Hospital Hamburg-Eppendorf, Centre for Experimental Medicine, Institute of Biochemistry and Molecular Biology I: Cellular Signal Transduction, Martinistr. 52, 20246 Hamburg, Germany. Tel.: 49-40-42803-2828. Fax: 49-40-42803-9880. email: guse{at}uke.uni-hamburg.de

The role of cyclic ADP-ribose in the amplification of subcellular and global Ca²⁺ signaling upon stimulation of P2Y purinergic receptors was studied in 3T3 fibroblasts. Either (1) 3T3 fibroblasts (CD38^- cells), (2) 3T3 fibroblasts preloaded by incubation with extracellular cyclic ADP-ribose (cADPR), (3) 3T3 fibroblasts microinjected with ryanodine, or (4) 3T3 fibroblasts transfected to express the ADP-ribosyl cyclase CD38 (CD38⁺ cells) were used. Both preincubation with cADPR and CD38 expression resulted in comparable intracellular amounts of cyclic ADP-ribose (42.3 ± 5.2 and 50.5 ± 8.0 pmol/mg protein). P2Y receptor stimulation of CD38^- cells yielded a small increase of intracellular Ca²⁺ concentration and a much higher Ca²⁺ signal in CD38-transfected cells, in cADPR-preloaded cells, or in cells microinjected with ryanodine. Confocal Ca²⁺ imaging revealed that stimulation of ryanodine receptors by cADPR or ryanodine amplified localized pacemaker Ca²⁺ signals with properties resembling Ca²⁺ quarks and triggered the propagation of such localized signals from the plasma membrane toward the internal environment, thereby initiating a global Ca²⁺ wave.

Key Words: cyclic ADP-ribose; Ca²⁺ signaling; 3T3 cell; CD38; signal transduction

Abbreviations used in this paper: cADPR, cyclic ADP-ribose; IP₃, D-myo-inositol 1,4,5-trisphosphate; IP₃R, IP₃ receptor; ROI, region of interest; RyR, ryanodine receptor.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Munoz, P., Mittelbrunn, M., de la Fuente, H., Perez-Martinez, M., Garcia-Perez, A., Ariza-Veguillas, A., Malavasi, F., Zubiaur, M., Sanchez-Madrid, F., Sancho, J. (2008). Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunologic synapse. Blood 111: 3653-3664 [Abstract] [Full Text]  
• Partida-Sanchez, S., Gasser, A., Fliegert, R., Siebrands, C. C., Dammermann, W., Shi, G., Mousseau, B. J., Sumoza-Toledo, A., Bhagat, H., Walseth, T. F., Guse, A. H., Lund, F. E. (2007). Chemotaxis of Mouse Bone Marrow Neutrophils and Dendritic Cells Is Controlled by ADP-Ribose, the Major Product Generated by the CD38 Enzyme Reaction. J. Immunol. 179: 7827-7839 [Abstract] [Full Text]  
• Steen, M., Kirchberger, T., Guse, A. H. (2007). NAADP Mobilizes Calcium from the Endoplasmic Reticular Ca2+ Store in T-lymphocytes. J. Biol. Chem. 282: 18864-18871 [Abstract] [Full Text]  
• Furuya, K., Sokabe, M., Furuya, S. (2005). Characteristics of subepithelial fibroblasts as a mechano-sensor in the intestine: cell-shape-dependent ATP release and P2Y1 signaling. J. Cell Sci. 118: 3289-3304 [Abstract] [Full Text]  
• Dammermann, W., Guse, A. H. (2005). Functional Ryanodine Receptor Expression Is Required for NAADP-mediated Local Ca2+ Signaling in T-lymphocytes. J. Biol. Chem. 280: 21394-21399 [Abstract] [Full Text]  
• Deshpande, D. A., White, T. A., Dogan, S., Walseth, T. F., Panettieri, R. A., Kannan, M. S. (2005). CD38/cyclic ADP-ribose signaling: role in the regulation of calcium homeostasis in airway smooth muscle. Am. J. Physiol. Lung Cell. Mol. Physiol. 288: L773-L788 [Abstract] [Full Text]  
• Guse, A. H., Gu, X., Zhang, L., Weber, K., Kramer, E., Yang, Z., Jin, H., Li, Q., Carrier, L., Zhang, L. (2005). A Minimal Structural Analogue of Cyclic ADP-ribose: SYNTHESIS AND CALCIUM RELEASE ACTIVITY IN MAMMALIAN CELLS. J. Biol. Chem. 280: 15952-15959 [Abstract] [Full Text]  
• Podesta, M., Benvenuto, F., Pitto, A., Figari, O., Bacigalupo, A., Bruzzone, S., Guida, L., Franco, L., Paleari, L., Bodrato, N., Usai, C., De Flora, A., Zocchi, E. (2005). Concentrative Uptake of Cyclic ADP-ribose Generated by BST-1+ Stroma Stimulates Proliferation of Human Hematopoietic Progenitors. J. Biol. Chem. 280: 5343-5349 [Abstract] [Full Text]  
• Puce, S., Basile, G., Bavestrello, G., Bruzzone, S., Cerrano, C., Giovine, M., Arillo, A., Zocchi, E. (2004). Abscisic Acid Signaling through Cyclic ADP-ribose in Hydroid Regeneration. J. Biol. Chem. 279: 39783-39788 [Abstract] [Full Text]  
• Kunerth, S., Langhorst, M. F., Schwarzmann, N., Gu, X., Huang, L., Yang, Z., Zhang, L., Mills, S. J., Zhang, L.-h., Potter, B. V.L., Guse, A. H. (2004). Amplification and propagation of pacemaker Ca2+ signals by cyclic ADP-ribose and the type 3 ryanodine receptor in T cells. J. Cell Sci. 117: 2141-2149 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents