scholarly journals Involvement of Transient Receptor Potential Cation Channel Member A1 activation in the irritation and pain response elicited by skin-lightening reagent hydroquinone

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Yan Tai ◽  
Chuan Wang ◽  
Zhihua Wang ◽  
Yi Liang ◽  
Junying Du ◽  
...  
2016 ◽  
Vol 9 (1) ◽  
Author(s):  
Jason Baek

When one reads the words ”heat vision,” it is common to imagine Superman flying through the air, blasting red beams from his eye sockets. Although this is a fairly creative image, the type of “heat vision” found in many snakes is different. When alluding to “heat vision” in snakes, one refers to the ability of certain snake species to sense heat through pit organs. These structures connect with a snake’s sense of touch, with the trigeminal nerves and ganglia being major components of this mechanism. Transient receptor potential cation channel, member A1, or PRTA1, is a protein found in the stems of trigeminal nerves. It is often asserted that the evolution of PRTA1 is directly connected to the evolution of infrared sensory pitbearing snakes. Quand une personne lit les mots ”vision de chaleur,” il est naturel que la première chose qui vient a tête est l’image de Superman qui vole dans le ciel avec des rayons rouges quit sortes de ses yeux. Bien que ceci est une image créative, le type de “vision de chaleur” qui se trouve dans les serpents est très différent. Lorsqu’on parle de “vision de chaleur” dans les serpents souvent on réfère à l’abilité que l’èspece de serpent peut sentir la chaleur à travers de ses organes. Ces structures on des connections avec le sens du toucher d’un serpent, avec les nerves trijumeau et le ganglion qui sont des composants major de cette méchanism. Le canal cationique potentiel de récepteur transitoire, membre A1, ou PRTA1, est un protéin qui se trouve dans les tuyaux des nerves trijumeau. Il est souvent affirmé que l’évolution du PRTA1 est directement connecté à l’évolution des serpents de puits avec sensorielle infrarouge.


Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 397
Author(s):  
Andras Szollosi

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.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Iordan Iordanov ◽  
Csaba Mihályi ◽  
Balázs Tóth ◽  
László Csanády

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.


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