TRPM2 and warmth sensation.
TRPM2 and warmth sensation.
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DOI：
10.1007/s00424-018-2139-7
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
McNaughton PA
中科院分区：
文献类型：
--
作者：
Tan CH;McNaughton PA
检测温暖和热量的能力对于所有动物的生存至关重要，这既是为了能够为生命必需的许多不同活动识别合适的热环境，也是为了避免极端温度造成的损害。属于 TRP 家族的几种离子通道可被无害的温暖或热量激活，因此是热探测器的候选者，但在完整动物中识别真正调节温暖和热探测的离子通道已被证明是有问题的。 TRPM2 最近已成为无害温暖检测器的候选者，因为它在感觉神经元中表达，当 TRPM2 被基因删除时，小鼠在温暖检测方面表现出缺陷。 TRPM2 是一种酶，含有连接到 C 端基序的热激活 TRP 离子通道结构域，衍生自线粒体 ADP 核糖焦磷酸酶，赋予通道对 ADP 核糖和活性氧（例如过氧化氢）的敏感性。仍有几个悬而未决的问题。雄性哺乳动物比雌性更喜欢凉爽的环境，但这种性别差异的分子基础尚不清楚。 TRPM2 在调节体温方面发挥作用，但是否还涉及其他体温检测机制？ TRPM2 在自主神经元中表达，但除了众所周知的自主神经元运动功能外，它是否还赋予感觉功能？ TRPM2被认为在免疫系统、疼痛和胰岛素分泌中发挥重要作用，但其机制尚不清楚。迄今为止，与 TRP 家族的许多其他成员相比，TRPM2 受到的关注较少，但在正常生理学和疾病病理学的关键靶标中迅速发挥着重要作用。
The abilities to detect warmth and heat are critical for the survival of all animals, both in order to be able to identify suitable thermal environments for the many different activities essential for life and to avoid damage caused by extremes of temperature. Several ion channels belonging to the TRP family are activated by non-noxious warmth or by heat and are therefore plausible candidates for thermal detectors, but identifying those that actually regulate warmth and heat detection in intact animals has proven problematic. TRPM2 has recently emerged as a likely candidate for the detector of non-noxious warmth, as it is expressed in sensory neurons, and mice show deficits in the detection of warmth when TRPM2 is genetically deleted. TRPM2 is a chanzyme, containing a thermally activated TRP ion channel domain attached to a C-terminal motif, derived from a mitochondrial ADP ribose pyrophosphatase, that confers on the channel sensitivity to ADP ribose and reactive oxygen species such as hydrogen peroxide. Several open questions remain. Male mammals prefer cooler environments than female, but the molecular basis of this sex difference is unknown. TRPM2 plays a role in regulating body temperature, but are other warmth-detecting mechanisms also involved? TRPM2 is expressed in autonomic neurons, but does it confer a sensory function in addition to the well-known motor functions of autonomic neurons? TRPM2 is thought to play important roles in the immune system, in pain and in insulin secretion, but the mechanisms are unclear. TRPM2 has to date received less attention than many other members of the TRP family but is rapidly assuming importance both in normal physiology and as a key target in disease pathology.
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