AUTHOR=Fliegert Ralf , Riekehr Winnie M. , Guse Andreas H. 

TITLE=Does Cyclic ADP-Ribose (cADPR) Activate the Non-selective Cation Channel TRPM2?

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.02018

DOI=10.3389/fimmu.2020.02018

ISSN=1664-3224

ABSTRACT=<p>TRPM2 is a non-selective, Ca<sup>2+</sup>-permeable cation channel widely expressed in immune cells. It is firmly established that the channel can be activated by intracellular adenosine 5′-diphosphoribose (ADPR). Until recent cryo-EM structures have exhibited an additional nucleotide binding site in the N-terminus of the channel, this activation was thought to occur via binding to a C-terminal domain of the channel that is highly homologous to the ADPR pyrophosphatase NudT9. Over the years it has been controversially discussed whether the Ca<sup>2+</sup> mobilizing second messenger cyclic ADP ribose (cADPR) might also directly activate Ca<sup>2+</sup> entry via TRPM2. Here we will review the status of this discussion.</p>