Project Details
Role of the purine nucleotide messengers cyclic ADP-ribose and ADP-ribose in T-lymphocyte biology
Applicant
Professor Dr. Andreas H. Guse
Subject Area
Pharmacology
Term
from 2009 to 2014
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 86975855
P2X7 and TRPM2 are cation channels expressed by T lymphocytes that are gated by extra- and intracellular adenine nucleotides, respectively. P2X7, in addition, mediates membrane permeability changes towards multiple substrates including nucleotides and drugs. Although increasing evidence points to a pivotal role of both channels in inflammation, their effects on T cells remain unclear. The primary goal of the current project is thus to characterize the roles of P2X7 and TRPM2 during the early events of T cell activation. To this end, we will use live cell Ca2+ and ATP imaging, HPLC, and patch-clamp techniques to study the roles of these channels in TCR signaling. Especially, we will test the hypothesis that 2`-deoxy-adenosine diphosphoribose (2´-deoxy-ADPR), instead of ADPR, is the major endogenous activating ligand of TRPM2, and characterize P2X7-induced changes in T cell permeability to nucleotides and other signaling molecules, thereby providing a link between the worlds of signaling by intra- and extracellular nucleotides. Characterization of the roles of P2X7 and TRPM2 in TCR signaling will provide the basis for assessing the potential of new therapeutic strategies aimed at targeting these two ion channels.
DFG Programme
Research Grants
Participating Person
Dr. Ralf Fliegert