Opportunistic activation of TRP receptors by endogenous lipids: exploiting lipidomics to understand TRP receptor cellular communication.
Opportunistic activation of TRP receptors by endogenous lipids: exploiting lipidomics to understand TRP receptor cellular communication.
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DOI：
10.1016/j.lfs.2012.11.008
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发表时间：
2013-03-19
期刊：
影响因子：
6.1
通讯作者：
Hollis, Jennifer L.
中科院分区：
文献类型：
--
作者：
Bradshaw, Heather B.;Raboune, Siham;Hollis, Jennifer L.
瞬时受体电位通道(TRPs)形成了一个无处不在的非选择性阳离子通道大家族，它们作为细胞传感器发挥作用，在许多情况下调节细胞内钙离子。激活这些色氨酸受体的内源性配体的鉴定仍在紧张的调查中，这些通道中的大多数仍然是“孤儿”。这些通道对各种外界刺激(如植物来源的脂类、温度变化和pH变化)的反应为它们作为细胞传感器的能力提供了一个框架，然而，直接激活的机制仍然存在很大的争论和研究。在内源性配体(主要是脂类)显示直接激活一个通道的情况下，已有多个配体被证明激活同一通道，这表明这些受体本质上是“混杂的”。一类日益增长的内源性脂质，N-酰基酰胺，其中最著名的是N-花生四烯基乙醇胺(内源性大麻素，ANANDAME)的脂类组学提供了一组新的配体，已被证明可以激活Trp家族的一些成员，并有可能使更多的成员去变形。在这里，有人认为，TRPV受体是更大的TRP家族的一个子集，由结构上相似的多种内源性脂类激活，是一个模型系统，推动我们理解许多Trp受体不是混杂的，而是本质上更具特征的“机会主义”；利用窄范围类似内源性脂类的结构相似性和生物合成。此外，这篇论文还将比较TRPC5的激活特性和一种“孤儿”脂质--N-棕榈酰甘氨酸的活性；进一步证明，旨在扩大我们对N-酰基酰胺家族知识的脂质组学有可能为色氨酸受体提供新的研究途径。
Transient receptor potential channels (TRPs) form a large family of ubiquitous non-selective cation channels that function as cellular sensors and in many cases regulate intracellular calcium. Identification of the endogenous ligands that activate these TRP receptors is still under intense investigation with the majority of these channels still remaining “orphans”. That these channels respond to a variety of external stimuli (e.g. plant-derived lipids, changes in temperature, and changes in pH) provides a framework for their abilities as cellular sensors, however, the mechanism of direct activation is still under much debate and research. In the cases where endogenous ligands (predominately lipids) have shown direct activation of a channel, multiple ligands have been shown to activate the same channel suggesting that these receptors are “promiscuous” in nature. Lipidomics of a growing class of endogenous lipids, N-acyl amides, the most famous of which is N-arachidonoyl ethanolamine (the endogenous cannabinoid, Anandamide) is providing a novel set of ligands that have been shown to activate some members of the TRP family and have the potential to deorphanize many more. Here it is argued that activation of TRPV receptors, a subset of the larger family of TRPs, by multiple endogenous lipids that are structurally analogous is a model system to drive our understanding that many TRP receptors are not promiscuous, but are more characteristically “opportunistic” in nature; exploiting the structural similarity and biosynthesis of a narrow range of analogous endogenous lipids. In addition, this manuscript will compare the activation properties of TRPC5 to the activity profile of an “orphan” lipid, N-palmitoyl glycine; further demonstrating that lipidomics aimed at expanding our knowledge of the family of N-acyl amides has the potential to provide novel avenues of research for TRP receptors.
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