| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Institute of Immunology, University Hospital, Hamburg, Germany;
The Jackson Laboratory, Bar Harbor, ME 04609;
Université Denis Diderot, Paris, France;
The Trudeau Institute, Saranac Lake, NY 12983; and
¶ University of California, San Francisco, CA 94143
ADP-ribosyltransferase-2 (ART2), a GPI-anchored, toxin-related ADP-ribosylating ectoenzyme, is prominently expressed by murine T cells but not by B cells. Upon exposure of T cells to NAD, the substrate for ADP-ribosylation, ART2 catalyzes ADP-ribosylation of the P2X7 purinoceptor and other functionally important cell surface proteins. This in turn activates P2X7 and induces exposure of phosphatidylserine and shedding of CD62L. CD38, a potent ecto-NAD-glycohydrolase, is strongly expressed by most B cells but only weakly by T cells. Following incubation with NAD, CD38-deficient splenocytes exhibited lower NAD-glycohydrolase activity and stronger ADP-ribosylation of cell surface proteins than their wild-type counterparts. Depletion of CD38high cells from wild-type splenocytes resulted in stronger ADP-ribosylation on the remaining cells. Similarly, treatment of total splenocytes with the CD38 inhibitor nicotinamide 2'-deoxy-2'-fluoroarabinoside adenine dinucleotide increased the level of cell surface ADP-ribosylation. Furthermore, the majority of T cells isolated from CD38-deficient mice "spontaneously" exposed phosphatidylserine and lacked CD62L, most likely reflecting previous encounter with ecto-NAD. Our findings support the notion that ecto-NAD functions as a signaling molecule following its release from cells by lytic or nonlytic mechanisms. ART2 can sense and translate the local concentration of ecto-NAD into corresponding levels of ADP-ribosylated cell surface proteins, whereas CD38 controls the level of cell surface protein ADP-ribosylation by limiting the substrate availability for ART2.
This article has been cited by other articles:
|
|
 |
|
  S. Hong, N. Schwarz, A. Brass, M. Seman, F. Haag, F. Koch-Nolte, W. P. Schilling, and G. R. Dubyak Differential Regulation of P2X7 Receptor Activation by Extracellular Nicotinamide Adenine Dinucleotide and Ecto-ADP-Ribosyltransferases in Murine Macrophages and T Cells J. Immunol., July 1, 2009; 183(1): 578 - 592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Scheuplein, N. Schwarz, S. Adriouch, C. Krebs, P. Bannas, B. Rissiek, M. Seman, F. Haag, and F. Koch-Nolte NAD+ and ATP Released from Injured Cells Induce P2X7-Dependent Shedding of CD62L and Externalization of Phosphatidylserine by Murine T Cells J. Immunol., March 1, 2009; 182(5): 2898 - 2908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Malavasi, S. Deaglio, A. Funaro, E. Ferrero, A. L. Horenstein, E. Ortolan, T. Vaisitti, and S. Aydin Evolution and Function of the ADP Ribosyl Cyclase/CD38 Gene Family in Physiology and Pathology Physiol Rev, July 1, 2008; 88(3): 841 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Mayo, J. Jacob-Hirsch, N. Amariglio, G. Rechavi, M.-J. Moutin, F. E. Lund, and R. Stein Dual Role of CD38 in Microglial Activation and Activation-Induced Cell Death J. Immunol., July 1, 2008; 181(1): 92 - 103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Adriouch, P. Bannas, N. Schwarz, R. Fliegert, A. H. Guse, M. Seman, F. Haag, and F. Koch-Nolte ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site FASEB J, March 1, 2008; 22(3): 861 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hong, A. Brass, M. Seman, F. Haag, F. Koch-Nolte, and G. R. Dubyak Lipopolysaccharide, IFN-{gamma}, and IFN-beta Induce Expression of the Thiol-Sensitive ART2.1 Ecto-ADP-Ribosyltransferase in Murine Macrophages J. Immunol., November 1, 2007; 179(9): 6215 - 6227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Koch-Nolte, J. Reyelt, B. Schossow, N. Schwarz, F. Scheuplein, S. Rothenburg, F. Haag, V. Alzogaray, A. Cauerhff, and F. A. Goldbaum Single domain antibodies from llama effectively and specifically block T cell ecto-ADP-ribosyltransferase ART2.2 in vivo FASEB J, November 1, 2007; 21(13): 3490 - 3498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Adriouch, S. Hubert, S. Pechberty, F. Koch-Nolte, F. Haag, and M. Seman NAD+ Released during Inflammation Participates in T Cell Homeostasis by Inducing ART2-Mediated Death of Naive T Cells In Vivo J. Immunol., July 1, 2007; 179(1): 186 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Liao and D. G. Puro NAD+-Induced Vasotoxicity in the Pericyte-Containing Microvasculature of the Rat Retina: Effect of Diabetes Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 5032 - 5038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Moreschi, S. Bruzzone, R. A. Nicholas, F. Fruscione, L. Sturla, F. Benvenuto, C. Usai, S. Meis, M. U. Kassack, E. Zocchi, et al. Extracellular NAD+ Is an Agonist of the Human P2Y11 Purinergic Receptor in Human Granulocytes J. Biol. Chem., October 20, 2006; 281(42): 31419 - 31429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. O. Hassa, S. S. Haenni, M. Elser, and M. O. Hottiger Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going? Microbiol. Mol. Biol. Rev., September 1, 2006; 70(3): 789 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-G. Chen, J. Chen, M. A. Osborne, H. D. Chapman, G. S. Besra, S. A. Porcelli, E. H. Leiter, S. B. Wilson, and D. V. Serreze CD38 Is Required for the Peripheral Survival of Immunotolerogenic CD4+ Invariant NK T Cells in Nonobese Diabetic Mice. J. Immunol., September 1, 2006; 177(5): 2939 - 2947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Deaglio, T. Vaisitti, S. Aydin, E. Ferrero, and F. Malavasi In-tandem insight from basic science combined with clinical research: CD38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia Blood, August 15, 2006; 108(4): 1135 - 1144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, Y.-G. Chen, P. C. Reifsnyder, W. H. Schott, C.-H. Lee, M. Osborne, F. Scheuplein, F. Haag, F. Koch-Nolte, D. V. Serreze, et al. Targeted Disruption of CD38 Accelerates Autoimmune Diabetes in NOD/Lt Mice by Enhancing Autoimmunity in an ADP-Ribosyltransferase 2-Dependent Fashion. J. Immunol., April 15, 2006; 176(8): 4590 - 4599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kawamura, F. Aswad, M. Minagawa, S. Govindarajan, and G. Dennert P2X7 Receptors Regulate NKT Cells in Autoimmune Hepatitis J. Immunol., February 15, 2006; 176(4): 2152 - 2160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zolkiewska Ecto-ADP-ribose Transferases: Cell-Surface Response to Local Tissue Injury Physiology, December 1, 2005; 20(6): 374 - 381. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
