HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 5, 2489-2496, February 3, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/5/2489    most recent M506525200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gasser, A. Articles by Guse, A. H. Search for Related Content PubMed PubMed Citation Articles by Gasser, A. Articles by Guse, A. H. Social Bookmarking                      What's this?

Activation of T Cell Calcium Influx by the Second Messenger ADP-ribose^*

Andreas Gasser, Günter Glassmeier, Ralf Fliegert, Matthias F. Langhorst¹, Stephan Meinke, Dörte Hein, Sylvia Krüger, Karin Weber, Inka Heiner^¶, Norman Oppenheimer^||, Jürgen R. Schwarz, and Andreas H. Guse²

From the University Medical Center Hamburg-Eppendorf, Center of Experimental Medicine, Institute of Biochemistry and Molecular Biology I: Cellular Signal Transduction and the Institute of Applied Physiology, D-20246 Hamburg, Germany, the ^¶Institute of Physiology, University Hospital of the Rheinisch-Westfälische Technische Hochschule Aachen, D-52057 Aachen, Germany and the ^||Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143

Stimulation of Jurkat T cells by high concentrations of concanavalin A (ConA) induced an elevation of the endogenous adenosine diphosphoribose (ADPR) concentration and an inward current significantly different from the Ca²⁺ release-activated Ca²⁺ current (I_CRAC). Electrophysiological characterization and activation of a similar current by infusion of ADPR indicated that the ConA-induced current is carried by TRPM2. Expression of TRPM2 in the plasma membrane of Jurkat T cells was demonstrated by reverse transcription-PCR, Western blot, and immunofluorescence. Inhibition of ADPR formation reduced ConA-mediated, but not store-operated, Ca²⁺ entry and prevented ConA-induced cell death of Jurkat cells. Moreover, gene silencing of TRPM2 abolished the ADPR- and ConA-mediated inward current. Thus, ADPR is a novel second messenger significantly involved in ConA-mediated cell death in T cells.

Received for publication, June 15, 2005 , and in revised form, November 18, 2005.

^* This study was supported by grants from the Deutsche Forschungsgemeinschaft (to A. H. G. and J. R. S) and from the Werner-Otto-Foundation, the Wellcome Trust, and the Gemeinnützige Hertie-Stiftung (all to A. H. G.). This article is based in part on doctoral studies by A. G. and R. F. in the faculties of Chemistry and Biology, University of Hamburg. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Present address: Developmental Neurobiology Group, Department of Biology, University of Konstanz, Germany.

² To whom correspondence should be addressed: University Medical Center Hamburg-Eppendorf, Center of Experimental Medicine, Institute of Biochemistry and Molecular Biology I: Cellular Signal Transduction, Martinistr. 52, D-20246 Hamburg, Germany. Tel.: 49-40-42803-2828; Fax: 49-40-42803-9880, E-mail: guse{at}uke.uni-hamburg.de.

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

This article has been cited by other articles:

				B. Buelow, Y. Song, and A. M. Scharenberg The Poly(ADP-ribose) Polymerase PARP-1 Is Required for Oxidative Stress-induced TRPM2 Activation in Lymphocytes J. Biol. Chem., September 5, 2008; 283(36): 24571 - 24583. [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]

				S. Dadsetan, L. Zakharova, T. F. Molinski, and A. F. Fomina Store-operated Ca2+ Influx Causes Ca2+ Release from the Intracellular Ca2+ Channels That Is Required for T Cell Activation J. Biol. Chem., May 2, 2008; 283(18): 12512 - 12519. [Abstract] [Full Text] [PDF]

				S. Partida-Sanchez, A. Gasser, R. Fliegert, C. C. Siebrands, W. Dammermann, G. Shi, B. J. Mousseau, A. Sumoza-Toledo, H. Bhagat, T. F. Walseth, et al. 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., December 1, 2007; 179(11): 7827 - 7839. [Abstract] [Full Text] [PDF]

				G. Shi, S. Partida-Sanchez, R. S. Misra, M. Tighe, M. T. Borchers, J. J. Lee, M. I. Simon, and F. E. Lund Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes J. Exp. Med., October 29, 2007; 204(11): 2705 - 2718. [Abstract] [Full Text] [PDF]

				W. Zhang, Q. Tong, K. Conrad, J. Wozney, J. Y. Cheung, and B. A. Miller Regulation of TRP channel TRPM2 by the tyrosine phosphatase PTPL1 Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1746 - C1758. [Abstract] [Full Text] [PDF]

				S. Bruzzone, G. Dodoni, N. Kaludercic, G. Basile, E. Millo, A. De Flora, F. Di Lisa, and E. Zocchi Mitochondrial Dysfunction Induced by a Cytotoxic Adenine Dinucleotide Produced by ADP-ribosyl Cyclases from cADPR J. Biol. Chem., February 16, 2007; 282(7): 5045 - 5052. [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]

				R. N. Carter, G. Tolhurst, G. Walmsley, M. Vizuete-Forster, N. Miller, and M. P. Mahaut-Smith Molecular and electrophysiological characterization of transient receptor potential ion channels in the primary murine megakaryocyte J. Physiol., October 1, 2006; 576(1): 151 - 162. [Abstract] [Full Text] [PDF]

				A. Gasser, S. Bruhn, and A. H. Guse Second Messenger Function of Nicotinic Acid Adenine Dinucleotide Phosphate Revealed by an Improved Enzymatic Cycling Assay J. Biol. Chem., June 23, 2006; 281(25): 16906 - 16913. [Abstract] [Full Text] [PDF]