Research ExplorerPublicationscADPR Does Not Activate TRPM2

cADPR Does Not Activate TRPM2

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cADPR Does Not Activate TRPM2. / Riekehr, Winnie Maria; Sander, Simon; Pick, Jelena; Tidow, Henning; Bauche, Andreas; Guse, Andreas H; Fliegert, Ralf.

In: INT J MOL SCI, Vol. 23, No. 6, 3163, 15.03.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Riekehr, WM, Sander, S, Pick, J, Tidow, H, Bauche, A, Guse, AH & Fliegert, R 2022, 'cADPR Does Not Activate TRPM2', INT J MOL SCI, vol. 23, no. 6, 3163. https://doi.org/10.3390/ijms23063163

APA

Riekehr, W. M., Sander, S., Pick, J., Tidow, H., Bauche, A., Guse, A. H., & Fliegert, R. (2022). cADPR Does Not Activate TRPM2. INT J MOL SCI, 23(6), [3163]. https://doi.org/10.3390/ijms23063163

Vancouver

Riekehr WM, Sander S, Pick J, Tidow H, Bauche A, Guse AH et al. cADPR Does Not Activate TRPM2. INT J MOL SCI. 2022 Mar 15;23(6). 3163. https://doi.org/10.3390/ijms23063163

Bibtex

@article{fa500e456f414bad89aff5037545b67f,
title = "cADPR Does Not Activate TRPM2",
abstract = "cADPR is a second messenger that releases Ca2+ from intracellular stores via the ryanodine receptor. Over more than 15 years, it has been controversially discussed whether cADPR also contributes to the activation of the nucleotide-gated cation channel TRPM2. While some groups have observed activation of TRPM2 by cADPR alone or in synergy with ADPR, sometimes only at 37 °C, others have argued that this is due to the contamination of cADPR by ADPR. The identification of a novel nucleotide-binding site in the N-terminus of TRPM2 that binds ADPR in a horseshoe-like conformation resembling cADPR as well as the cADPR antagonist 8-Br-cADPR, and another report that demonstrates activation of TRPM2 by binding of cADPR to the NUDT9H domain raised the question again and led us to revisit the topic. Here we show that (i) the N-terminal MHR1/2 domain and the C-terminal NUDT9H domain are required for activation of human TRPM2 by ADPR and 2'-deoxy-ADPR (2dADPR), (ii) that pure cADPR does not activate TRPM2 under a variety of conditions that have previously been shown to result in channel activation, (iii) the cADPR antagonist 8-Br-cADPR also inhibits activation of TRPM2 by ADPR, and (iv) cADPR does not bind to the MHR1/2 domain of TRPM2 while ADPR does.",
keywords = "Binding Sites, Calcium/metabolism, Calcium Signaling, Cyclic ADP-Ribose/metabolism, Humans, TRPM Cation Channels/metabolism",
author = "Riekehr, {Winnie Maria} and Simon Sander and Jelena Pick and Henning Tidow and Andreas Bauche and Guse, {Andreas H} and Ralf Fliegert",
year = "2022",
month = mar,
day = "15",
doi = "10.3390/ijms23063163",
language = "English",
volume = "23",
journal = "INT J MOL SCI",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "6",

}

RIS

TY - JOUR

T1 - cADPR Does Not Activate TRPM2

AU - Riekehr, Winnie Maria

AU - Sander, Simon

AU - Pick, Jelena

AU - Tidow, Henning

AU - Bauche, Andreas

AU - Guse, Andreas H

AU - Fliegert, Ralf

PY - 2022/3/15

Y1 - 2022/3/15

N2 - cADPR is a second messenger that releases Ca2+ from intracellular stores via the ryanodine receptor. Over more than 15 years, it has been controversially discussed whether cADPR also contributes to the activation of the nucleotide-gated cation channel TRPM2. While some groups have observed activation of TRPM2 by cADPR alone or in synergy with ADPR, sometimes only at 37 °C, others have argued that this is due to the contamination of cADPR by ADPR. The identification of a novel nucleotide-binding site in the N-terminus of TRPM2 that binds ADPR in a horseshoe-like conformation resembling cADPR as well as the cADPR antagonist 8-Br-cADPR, and another report that demonstrates activation of TRPM2 by binding of cADPR to the NUDT9H domain raised the question again and led us to revisit the topic. Here we show that (i) the N-terminal MHR1/2 domain and the C-terminal NUDT9H domain are required for activation of human TRPM2 by ADPR and 2'-deoxy-ADPR (2dADPR), (ii) that pure cADPR does not activate TRPM2 under a variety of conditions that have previously been shown to result in channel activation, (iii) the cADPR antagonist 8-Br-cADPR also inhibits activation of TRPM2 by ADPR, and (iv) cADPR does not bind to the MHR1/2 domain of TRPM2 while ADPR does.

AB - cADPR is a second messenger that releases Ca2+ from intracellular stores via the ryanodine receptor. Over more than 15 years, it has been controversially discussed whether cADPR also contributes to the activation of the nucleotide-gated cation channel TRPM2. While some groups have observed activation of TRPM2 by cADPR alone or in synergy with ADPR, sometimes only at 37 °C, others have argued that this is due to the contamination of cADPR by ADPR. The identification of a novel nucleotide-binding site in the N-terminus of TRPM2 that binds ADPR in a horseshoe-like conformation resembling cADPR as well as the cADPR antagonist 8-Br-cADPR, and another report that demonstrates activation of TRPM2 by binding of cADPR to the NUDT9H domain raised the question again and led us to revisit the topic. Here we show that (i) the N-terminal MHR1/2 domain and the C-terminal NUDT9H domain are required for activation of human TRPM2 by ADPR and 2'-deoxy-ADPR (2dADPR), (ii) that pure cADPR does not activate TRPM2 under a variety of conditions that have previously been shown to result in channel activation, (iii) the cADPR antagonist 8-Br-cADPR also inhibits activation of TRPM2 by ADPR, and (iv) cADPR does not bind to the MHR1/2 domain of TRPM2 while ADPR does.

KW - Binding Sites

KW - Calcium/metabolism

KW - Calcium Signaling

KW - Cyclic ADP-Ribose/metabolism

KW - Humans

KW - TRPM Cation Channels/metabolism

U2 - 10.3390/ijms23063163

DO - 10.3390/ijms23063163

M3 - SCORING: Journal article

C2 - 35328585

VL - 23

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 6

M1 - 3163

ER -