scholarly journals Shear stress activates monovalent cation channel transient receptor potential melastatin subfamily 4 in rat atrial myocytes via type 2 inositol 1,4,5-trisphosphate receptors and Ca2+release

2016 ◽  
Vol 594 (11) ◽  
pp. 2985-3004 ◽  
Author(s):  
Min-Jeong Son ◽  
Joon-Chul Kim ◽  
Sung Woo Kim ◽  
Bojjibabu Chidipi ◽  
Jeyaraj Muniyandi ◽  
...  
Keyword(s):  
Shear Stress ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Monovalent Cation ◽  
Cation Channel ◽  
Atrial Myocytes ◽  
Transient Receptor Potential Melastatin ◽  
Inositol 1,4,5 Trisphosphate ◽  
Transient Receptor

scholarly journals Two Decades of Evolution of Our Understanding of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 397
Author(s):  
Andras Szollosi
Keyword(s):  
Structure Function ◽  
Cell Activation ◽  
Transient Receptor Potential ◽  
Immune Cell ◽  
Receptor Potential ◽  
Cation Channel ◽  
Biophysical Properties ◽  
Vast Number ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

The transient receptor potential melastatin (TRPM) family belongs to the superfamily of TRP ion channels. It consists of eight family members that are involved in a plethora of cellular functions. TRPM2 is a homotetrameric Ca2+-permeable cation channel activated upon oxidative stress and is important, among others, for body heat control, immune cell activation and insulin secretion. Invertebrate TRPM2 proteins are channel enzymes; they hydrolyze the activating ligand, ADP-ribose, which is likely important for functional regulation. Since its cloning in 1998, the understanding of the biophysical properties of the channel has greatly advanced due to a vast number of structure–function studies. The physiological regulators of the channel have been identified and characterized in cell-free systems. In the wake of the recent structural biochemistry revolution, several TRPM2 cryo-EM structures have been published. These structures have helped to understand the general features of the channel, but at the same time have revealed unexplained mechanistic differences among channel orthologues. The present review aims at depicting the major research lines in TRPM2 structure-function. It discusses biophysical properties of the pore and the mode of action of direct channel effectors, and interprets these functional properties on the basis of recent three-dimensional structural models.

scholarly journals The proposed channel-enzyme transient receptor potential melastatin 2 does not possess ADP ribose hydrolase activity

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Iordan Iordanov ◽  
Csaba Mihályi ◽  
Balázs Tóth ◽  
László Csanády
Keyword(s):  
Cell Death ◽  
Insulin Secretion ◽  
Transient Receptor Potential ◽  
Channel Gating ◽  
Receptor Potential ◽  
Cation Channel ◽  
Chimeric Proteins ◽  
Transient Receptor Potential Melastatin ◽  
Biochemical Studies ◽  
Transient Receptor

Transient Receptor Potential Melastatin 2 (TRPM2) is a Ca2+-permeable cation channel essential for immunocyte activation, insulin secretion, and postischemic cell death. TRPM2 is activated by ADP ribose (ADPR) binding to its C-terminal cytosolic NUDT9-homology (NUDT9H) domain, homologous to the soluble mitochondrial ADPR pyrophosphatase (ADPRase) NUDT9. Reported ADPR hydrolysis classified TRPM2 as a channel-enzyme, but insolubility of isolated NUDT9H hampered further investigations. Here we developed a soluble NUDT9H model using chimeric proteins built from complementary polypeptide fragments of NUDT9H and NUDT9. When expressed in E.coli, chimeras containing up to ~90% NUDT9H sequence remained soluble and were affinity-purified. In ADPRase assays the conserved Nudix-box sequence of NUDT9 proved essential for activity (kcat~4-9s-1), that of NUDT9H did not support catalysis. Replacing NUDT9H in full-length TRPM2 with soluble chimeras retained ADPR-dependent channel gating (K1/2~1-5 μM), confirming functionality of chimeric domains. Thus, TRPM2 is not a 'chanzyme'. Chimeras provide convenient soluble NUDT9H models for structural/biochemical studies.

scholarly journals Transient receptor potential melastatin 2 governs stress-induced depressive-like behaviors

2019 ◽  
Vol 116 (5) ◽  
pp. 1770-1775 ◽  
Author(s):  
Seung Yeon Ko ◽  
Sung Eun Wang ◽  
Han Kyu Lee ◽  
Sungsin Jo ◽  
Jinil Han ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Synaptic Function ◽  
Tissue Samples ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
The Brain ◽  
Synapsin 1

Major depressive disorder (MDD) is a devastating disease that arises in a background of environmental risk factors, such as chronic stress, that produce reactive oxygen species (ROS) in the brain. The chronic stress-induced ROS production involves Ca2+ signals; however, the mechanism is poorly understood. Transient receptor potential melastatin type 2 (TRPM2) is a Ca2+-permeable cation channel that is highly expressed in the brain. Here we show that in animal models of chronic unpredictable stress (CUS), deletion of TRPM2 (Trpm2−/−) produces antidepressant-like behaviors in mice. This phenotype correlates with reduced ROS, ROS-induced calpain activation, and enhanced phosphorylation of two Cdk5 targets including synapsin 1 and histone deacetylase 5 that are linked to synaptic function and gene expression, respectively. Moreover, TRPM2 mRNA expression is increased in hippocampal tissue samples from patients with MDD. Our findings suggest that TRPM2 is a key agent in stress-induced depression and a possible target for treating depression.

scholarly journals Disease-associated mutations in TRPM3 render the channel overactive via two distinct mechanisms

2020 ◽  
Author(s):  
Siyuan Zhao ◽  
Yevgen Yudin ◽  
Tibor Rohacs
Keyword(s):  
Intellectual Disability ◽  
Therapeutic Intervention ◽  
Room Temperature ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cation Channel ◽  
Transient Receptor Potential Melastatin ◽  
Heat Activation ◽  
Transient Receptor ◽  
Potential Therapeutic Intervention

ABSTRACTTransient Receptor Potential Melastatin 3 (TRPM3) is a Ca2+ permeable non-selective cation channel activated by heat and chemical agonists such as pregnenolone sulfate and CIM0216. TRPM3 mutations in humans were recently reported to be associated with intellectual disability and epilepsy; the functional effects of those mutations however were not reported. Here we show that both disease-associated mutations of TRPM3 render the channel overactive, but likely via different mechanisms. The Val to Met substitution in the S4-S5 loop induced a larger increase in basal activity and agonist sensitivity at room temperature than the Pro to Gln substitution in the extracellular segment of S6. In contrast, heat activation was increased more by the S6 mutant than by the S4-S5 segment mutant. Both mutants were inhibited by the TRPM3 antagonist primidone, suggesting a potential therapeutic intervention to treat this disease.

scholarly journals Aldosterone signaling through transient receptor potential melastatin 7 cation channel (TRPM7) and its α-kinase domain

2013 ◽  
Vol 25 (11) ◽  
pp. 2163-2175 ◽  
Author(s):  
Alvaro Yogi ◽  
Glaucia E. Callera ◽  
Sarah O'Connor ◽  
Tayze T. Antunes ◽  
William Valinsky ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Kinase Domain ◽  
Cation Channel ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

scholarly journals Crosstalk Between Vascular Redox and Calcium Signaling in Hypertension Involves TRPM2 (Transient Receptor Potential Melastatin 2) Cation Channel

Hypertension ◽  
2020 ◽  
Vol 75 (1) ◽  
pp. 139-149 ◽  
Author(s):  
Rhéure Alves-Lopes ◽  
Karla B. Neves ◽  
Aikaterini Anagnostopoulou ◽  
Francisco J. Rios ◽  
Silvia Lacchini ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cation Channel ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

scholarly journals Disease-associated mutations in the human TRPM3 render the channel overactive via two distinct mechanisms

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Siyuan Zhao ◽  
Yevgen Yudin ◽  
Tibor Rohacs
Keyword(s):  
Intellectual Disability ◽  
Therapeutic Intervention ◽  
Room Temperature ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cation Channel ◽  
Transient Receptor Potential Melastatin ◽  
Heat Activation ◽  
Transient Receptor ◽  
Potential Therapeutic Intervention

Transient Receptor Potential Melastatin 3 (TRPM3) is a Ca2+ permeable non-selective cation channel activated by heat and chemical agonists such as pregnenolone sulfate and CIM0216. TRPM3 mutations in humans were recently reported to be associated with intellectual disability and epilepsy; the functional effects of those mutations, however, were not reported. Here, we show that both disease-associated mutations in the human TRPM3 render the channel overactive, but likely via different mechanisms. The Val to Met substitution in the S4-S5 loop induced a larger increase in basal activity and agonist sensitivity at room temperature than the Pro to Gln substitution in the extracellular segment of S6. In contrast, heat activation was increased more by the S6 mutant than by the S4-S5 segment mutant. Both mutants were inhibited by the TRPM3 antagonist primidone, suggesting a potential therapeutic intervention to treat this disease.

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