Activation of T cell calcium influx by the second messenger ADP-ribose.
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.
Gasser
Andreas
A
University Medical Center Hamburg-Eppendorf, Center of Experimental Medicine, Institute of Biochemistry and Molecular Biology I: Cellular Signal Transduction.
Glassmeier
Günter
G
Fliegert
Ralf
R
Langhorst
Matthias F
MF
Meinke
Stephan
S
Hein
Dörte
D
Krüger
Sylvia
S
Weber
Karin
K
Heiner
Inka
I
Oppenheimer
Norman
N
Schwarz
Jürgen R
JR
Guse
Andreas H
AH
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism* / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death; D003208:Concanavalin A / Q000494:pharmacology; D004594:Electrophysiology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D015290:Second Messenger Systems / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D003208:Concanavalin A; D000246:Adenosine Diphosphate Ribose; D002118:Calcium