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

Front Immunol. 2020 Aug 11:11:2018. doi: 10.3389/fimmu.2020.02018. eCollection 2020.

Abstract

TRPM2 is a non-selective, Ca2+-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 Ca2+ mobilizing second messenger cyclic ADP ribose (cADPR) might also directly activate Ca2+ entry via TRPM2. Here we will review the status of this discussion.

Keywords: TRPM2; cADPR; calcium; ion channel; signal transduction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cyclic ADP-Ribose / metabolism*
  • Humans
  • Protein Binding
  • Signal Transduction
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism*

Substances

  • TRPM Cation Channels
  • TRPM2 protein, human
  • Cyclic ADP-Ribose
  • Calcium