Direct Gating of the TRPM2 Channel by cADPR via Specific Interactions with the ADPR Binding Pocket

Yu, Peilin; Liu, Zhenming; Yu, Xiafei; Ye, Peiwu; Liu, Huan; Xue, Xiwen; Yang, Lixin; Li, Zhongtang; Wu, Yang Chang; Fang, Cheng; Zhao, Yong; Yang, Fan; Luo, Jian; Jiang, Lin‐Hua; Zhang, Liangren; Zhang, Lihe; Yang, Wei

doi:10.1016/j.celrep.2019.05.067

Cited by 57 publications

(52 citation statements)

References 50 publications

(68 reference statements)

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“…Cyclic ADP ribose (cADPR) can also directly activate human TRPM2, but the EC 50 of cADPR for activation of TRPM2 is much higher than that of ADPR. This is in spite of the fact that the binding affinity of cADPR to the NUDT9-H domain is higher than that of ADPR [39]. cADPR binds to the same pocket of NUDT9-H that binds ADPR, but the interaction pattern of ADPR and cADPR with the binding sites are different [39].…”

Section: Trpm2mentioning

confidence: 96%

“…This is in spite of the fact that the binding affinity of cADPR to the NUDT9-H domain is higher than that of ADPR [39]. cADPR binds to the same pocket of NUDT9-H that binds ADPR, but the interaction pattern of ADPR and cADPR with the binding sites are different [39]. It should be noted that some batches of commercially available cADPR contain 25-50% ADPR as contaminant.…”

Section: Trpm2mentioning

confidence: 98%

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Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Islam

2020

Cells

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Insulin secretion from the β-cells of the islets of Langerhans is triggered mainly by nutrients such as glucose, and incretin hormones such as glucagon-like peptide-1 (GLP-1). The mechanisms of the stimulus-secretion coupling involve the participation of the key enzymes that metabolize the nutrients, and numerous ion channels that mediate the electrical activity. Several members of the transient receptor potential (TRP) channels participate in the processes that mediate the electrical activities and Ca2+ oscillations in these cells. Human β-cells express TRPC1, TRPM2, TRPM3, TRPM4, TRPM7, TRPP1, TRPML1, and TRPML3 channels. Some of these channels have been reported to mediate background depolarizing currents, store-operated Ca2+ entry (SOCE), electrical activity, Ca2+ oscillations, gene transcription, cell-death, and insulin secretion in response to stimulation by glucose and GLP1. Different channels of the TRP family are regulated by one or more of the following mechanisms: activation of G protein-coupled receptors, the filling state of the endoplasmic reticulum Ca2+ store, heat, oxidative stress, or some second messengers. This review briefly compiles our current knowledge about the molecular mechanisms of regulations, and functions of the TRP channels in the β-cells, the α-cells, and some insulinoma cell lines.

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Section: Trpm2mentioning

confidence: 96%

Section: Trpm2mentioning

confidence: 98%

Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Islam

2020

Cells

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“…The TRPM2 channel belongs to the superfamily of transient receptor potential (TRP) channels and is a tetrameric Ca 2+ ‐permeable non‐selective cation channel that is gated by intracellular ADP‐ribose (ADPR) and cyclic ADPR . Intracellular Ca 2+ can bind to and activate the TRPM2 channels, and warm temperature (≥35°C) can also induce the TRPM2 channel opening independently of, and more often in synergy with, ADPR or cyclic ADPR .…”

Section: Trpm2 Channel As a Common Molecular Mechanism Mediating Ros‐mentioning

confidence: 99%

“…The TRPM2 channel belongs to the superfamily of transient receptor potential (TRP) channels [15][16][17][18] and is a tetrameric Ca 2+ -permeable non-selective cation channel that is gated by intracellular ADP-ribose (ADPR) and cyclic ADPR. [19][20][21][22][23][24][25] Intracellular Ca 2+ can bind to and activate the TRPM2 channels, 26 and warm temperature (≥35°C) can also induce the TRPM2 channel opening independently of, and more often in synergy with, ADPR or cyclic ADPR. 27,28 The TRPM2 channel can be potently activated after exposure to pathologically relevant concentrations of ROS, which is thought to stimulate ADPR generation via poly(ADPR) polymerase (PARP), particularly PARP-1, and poly(ADRP) glycohydrolase (PARG) in the nucleus, and also via NADase in the mitochondria.…”

Section: Trpmchannel a S A Common Molecul Ar Mechanis M Mediating Rmentioning

confidence: 99%

TRPM2 channel: A novel target for alleviating ischaemia‐reperfusion, chronic cerebral hypo‐perfusion and neonatal hypoxic‐ischaemic brain damage

Mai

Mankoo

Wei

et al. 2019

J Cellular Molecular Medi

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The transient receptor potential melastatin‐related 2 (TRPM2) channel, a reactive oxygen species (ROS)‐sensitive cation channel, has been well recognized for being an important and common mechanism that confers the susceptibility to ROS‐induced cell death. An elevated level of ROS is a salient feature of ischaemia‐reperfusion, chronic cerebral hypo‐perfusion and neonatal hypoxia‐ischaemia. The TRPM2 channel is expressed in hippocampus, cortex and striatum, the brain regions that are critical for cognitive functions. In this review, we examine the recent studies that combine pharmacological and/or genetic interventions with using in vitro and in vivo models to demonstrate a crucial role of the TRPM2 channel in brain damage by ischaemia‐reperfusion, chronic cerebral hypo‐perfusion and neonatal hypoxic‐ischaemia. We also discuss the current understanding of the underlying TRPM2‐dependent cellular and molecular mechanisms. These new findings lead to the hypothesis of targeting the TRPM2 channel as a potential novel therapeutic strategy to alleviate brain damage and cognitive dysfunction caused by these conditions.

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“…The TRPM2 channel, member of the mammalian TRP channel superfamily, is a Ca 2+ -permeable cationic channel gated by intracellular ADP-ribose (ADPR) and related compounds (Perraud et al, 2001;Yu et al, 2017Yu et al, , 2019. The TRPM2 channel is highly sensitive to ROS due to the potent capacity of ROS to promote ADPR generation (Jiang et al, 2010).…”

Section: Perspective On Roles Of Oxidative Stress and Trpm2 Channel Imentioning

confidence: 99%

Predisposition to Alzheimer’s and Age-Related Brain Pathologies by PM2.5 Exposure: Perspective on the Roles of Oxidative Stress and TRPM2 Channel

et al. 2020

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Accumulating epidemiological evidence supports that chronic exposure to ambient fine particular matters of <2.5 µm (PM2.5) predisposes both children and adults to Alzheimer's disease (AD) and age-related brain damage leading to dementia. There is also experimental evidence to show that PM2.5 exposure results in early onset of AD-related pathologies in transgenic AD mice and development of AD-related and age-related brain pathologies in healthy rodents. Studies have also documented that PM2.5 exposure causes AD-linked molecular and cellular alterations, such as mitochondrial dysfunction, synaptic deficits, impaired neurite growth, neuronal cell death, glial cell activation, neuroinflammation, and neurovascular dysfunction, in addition to elevated levels of amyloid β (Aβ) and tau phosphorylation. Oxidative stress and the oxidative stress-sensitive TRPM2 channel play important roles in mediating multiple molecular and cellular alterations that underpin AD-related cognitive dysfunction. Documented evidence suggests critical engagement of oxidative stress and TRPM2 channel activation in various PM2.5-induced cellular effects. Here we discuss recent studies that favor causative relationships of PM2.5 exposure to increased AD prevalence and AD-and age-related pathologies, and raise the perspective on the roles of oxidative stress and the TRPM2 channel in mediating PM2.5-induced predisposition to AD and age-related brain damage.

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Direct Gating of the TRPM2 Channel by cADPR via Specific Interactions with the ADPR Binding Pocket

Cited by 57 publications

References 50 publications

Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

TRPM2 channel: A novel target for alleviating ischaemia‐reperfusion, chronic cerebral hypo‐perfusion and neonatal hypoxic‐ischaemic brain damage

Predisposition to Alzheimer’s and Age-Related Brain Pathologies by PM2.5 Exposure: Perspective on the Roles of Oxidative Stress and TRPM2 Channel

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