Fliegert Ralf, Riekehr Winnie M, Guse Andreas H
The Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Front Immunol. 2020 Aug 11;11:2018. doi: 10.3389/fimmu.2020.02018. eCollection 2020.
TRPM2 is a non-selective, Ca-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 mobilizing second messenger cyclic ADP ribose (cADPR) might also directly activate Ca entry via TRPM2. Here we will review the status of this discussion.
瞬时受体电位阳离子通道M2型（TRPM2）是一种非选择性、钙离子通透的阳离子通道，在免疫细胞中广泛表达。现已明确该通道可被细胞内的5'-二磷酸腺苷核糖（ADPR）激活。直到最近的冷冻电镜结构显示该通道的N端存在一个额外的核苷酸结合位点，此前人们一直认为这种激活是通过与通道的C端结构域结合而发生的，该结构域与ADPR焦磷酸酶NudT9高度同源。多年来，关于钙离子动员第二信使环ADP核糖（cADPR）是否也可能直接通过TRPM2激活钙离子内流一直存在争议。在此我们将综述这一讨论的现状。
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