Phosphoinositide regulation of TRPV1 revisited.
Phosphoinositide regulation of TRPV1 revisited.
复制标题
DOI：
10.1007/s00424-015-1695-3
复制
发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Rohacs T
中科院分区：
文献类型：
--
作者：
Rohacs T
对辣椒素敏感的瞬时受体电位香草蛋白1离子通道（TRPV1）受质膜磷酸肌苷的调控。这些脂质对该通道的影响一直存在争议。最近的一些文章重新点燃了这场争论，并提出了将一些数据放在一个连贯的画面中的解决方案。本文综述了这一课题的相关文献，并对磷脂酰肌醇4,5-二磷酸[PI(4,5)P2或PIP2]对TRPV1的各种作用的实验证据进行了详细和批判性的讨论。我们得出结论，PI(4,5)P2及其潜在的前体PI(4)P是TRPV1的正辅因子，通过与通道的直接相互作用起作用，并且在辣椒素诱导的脱敏过程中，Ca2+诱导的磷脂酶Cδ异构体（PLCδ）激活使它们的消耗限制了通道的活性。其他带负电荷的脂质在较高浓度下也可以支持通道活动，这可以解释文献中的一些争议。在一些实验环境中，PI(4,5)P2也部分抑制通道活性，这种抑制对PLCβ激活的缓解可能有助于致敏。PI(4,5)P2的负作用更有争议，其机制也不太清楚。来自TRPV和TRPC家族的其他TRP通道也可能受到磷酸肌苷的类似双重调控，因此TRPV1调控的复杂性并非该通道所独有。
The heat- and capsaicin-sensitive Transient Receptor Potential Vanilloid 1 ion channel (TRPV1) is regulated by plasma membrane phosphoinositides. The effects of these lipids on this channel have been controversial. Recent articles re-ignited the debate and also offered resolution to place some of the data in a coherent picture. This review summarizes the literature on this topic and provides a detailed and critical discussion on the experimental evidence for the various effects of phosphatidylinositol 4,5-bisphosphayte [PI(4,5)P2 or PIP2] on TRPV1. We conclude that PI(4,5)P2 and potentially its precursor PI(4)P are positive cofactors for TRPV1, acting via direct interaction with the channel, and their depletion by Ca2+-induced activation of phospholipase Cδ isoforms (PLCδ) limits channel activity during capsaicin-induced desensitization. Other negatively charged lipids at higher concentrations can also support channel activity, which may explain some controversies in the literature. PI(4,5)P2 also partially inhibits channel activity in some experimental settings, and relief from this inhibition upon PLCβ activation may contribute to sensitization. The negative effect of PI(4,5)P2 is more controversial and its mechanism is less well understood. Other TRP channels from the TRPV and TRPC families may also undergo similar dual regulation by phosphoinositides, thus the complexity of TRPV1 regulation is not unique to this channel.