English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

NAADP-mediated Ca2+ signaling via type 1 ryanodine receptor in T cells revealed by a synthetic NAADP antagonist

MPS-Authors
/persons/resource/persons38793

Cordiglieri,  C.
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

/persons/resource/persons39014

Odoardi,  F.
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

/persons/resource/persons38918

Kawakami,  N.
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

/persons/resource/persons38805

Dornmair,  K.
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

/persons/resource/persons38835

Flügel,  A.
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)
Supplementary Material (public)
There is no public supplementary material available
Citation

Dammermann, W., Zhang, B., Nebel, M., Cordiglieri, C., Odoardi, F., Kirchberger, T., et al. (2009). NAADP-mediated Ca2+ signaling via type 1 ryanodine receptor in T cells revealed by a synthetic NAADP antagonist. Proceedings of the National Academy of Sciences of the United States of America, 106(26), 10678-10683.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0012-206C-A
Abstract
The nucleotide NAADP was recently discovered as a second messenger involved in the initiation and propagation of Ca2+ signaling in lymphoma T cells, but its impact on primary T cell function is still unknown. An optimized, synthetic, small molecule inhibitor of NAADP action, termed BZ194, was designed and synthesized. BZ194 neither interfered with Ca2+ mobilization by D-myo-inositol 1,4,5-trisphosphate or cyclic ADP-ribose nor with capacitative Ca2+ entry. BZ194 specifically and effectively blocked NAADP-stimulated [H-3] ryanodine binding to the purified type 1 ryanodine receptor. Further, in intact T cells, Ca2+ mobilization evoked by NAADP or by formation of the immunological synapse between primary effector T cells and astrocytes was inhibited by BZ194. Downstream events of Ca2+ mobilization, such as nuclear translocation of "nuclear factor of activated T cells" (NFAT), T cell receptor-driven interleukin-2 production, and proliferation in antigen-experienced CD4(+) effector T cells, were attenuated by the NAADP antagonist. Taken together, specific inhibition of the NAADP signaling pathway constitutes a way to specifically and effectively modulate T-cell activation and has potential in the therapy of autoimmune diseases.