The Role of TRP Proteins in Mast Cells.
The Role of TRP Proteins in Mast Cells.
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DOI：
10.3389/fimmu.2012.00150
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发表时间：
2012
影响因子：
7.3
通讯作者：
Tsvilovskyy V
中科院分区：
文献类型：
--
作者：
Freichel M;Almering J;Tsvilovskyy V
瞬时受体电位（TRP）蛋白形成阳离子通道，所述阳离子通道通过显著不同的机制来调节，包括多种细胞表面受体、温度、pH和渗透压、胞质游离Ca 2+浓度（[Ca 2 +]i）的变化，以及通过磷酸肌醇调节，所述磷酸肌醇使它们成为用于微调体内许多细胞和系统过程的多模态传感器。在哺乳动物中鉴定的28种TRP蛋白分为六个亚家族：TRPC、TRPV、TRPM、TRPA、TRPML和TRPP。当被激活时，它们有助于细胞去极化和Ca2+进入。在肥大细胞中，[Ca 2 +]i的增加是其生物活性的基础，并且描述了Ca 2+和其他阳离子的几种进入途径，包括Ca 2+释放激活的Ca 2+（CRAC）通道。与其他非兴奋细胞一样，TRP通道可以作为Ca 2+传导通道复合物的组成部分直接通过质膜促进Ca 2+内流，或者通过改变膜电位和调节独立Ca 2+进入通道的Ca 2+进入驱动力来间接促进Ca 2+内流。在这里，我们总结了目前的知识，个别色氨酸基因的表达与大多数的28个成员尚未确定在不同的肥大细胞模型，我们强调的机制，他们如何能够调节肥大细胞的功能。由于TRP家族的大多数成员仍然缺乏特异性激动剂或阻断剂，因此研究其功能和激活模式仍然依赖于使用遗传方法和转基因动物的实验。RNAi方法表明TRPC 1、TRPC 5和TRPM 7在肥大细胞衍生的细胞系或原代肥大细胞中具有功能性作用，并且使用Trp基因敲除小鼠的研究揭示了TRPM 4在肥大细胞活化和肥大细胞介导的皮肤过敏反应中的关键作用，而冷和薄荷醇活化的TRPM 8通道的直接作用似乎不太可能至少在小鼠中发展为冷性荨麻疹。
Transient receptor potential (TRP) proteins form cation channels that are regulated through strikingly diverse mechanisms including multiple cell surface receptors, changes in temperature, in pH and osmolarity, in cytosolic free Ca2+ concentration ([Ca2+]i), and by phosphoinositides which makes them polymodal sensors for fine tuning of many cellular and systemic processes in the body. The 28 TRP proteins identified in mammals are classified into six subfamilies: TRPC, TRPV, TRPM, TRPA, TRPML, and TRPP. When activated, they contribute to cell depolarization and Ca2+ entry. In mast cells, the increase of [Ca2+]i is fundamental for their biological activity, and several entry pathways for Ca2+ and other cations were described including Ca2+ release activated Ca2+ (CRAC) channels. Like in other non-excitable cells, TRP channels could directly contribute to Ca2+ influx via the plasma membrane as constituents of Ca2+ conducting channel complexes or indirectly by shifting the membrane potential and regulation of the driving force for Ca2+ entry through independent Ca2+ entry channels. Here, we summarize the current knowledge about the expression of individual Trp genes with the majority of the 28 members being yet identified in different mast cell models, and we highlight mechanisms how they can regulate mast cell functions. Since specific agonists or blockers are still lacking for most members of the TRP family, studies to unravel their function and activation mode still rely on experiments using genetic approaches and transgenic animals. RNAi approaches suggest a functional role for TRPC1, TRPC5, and TRPM7 in mast cell derived cell lines or primary mast cells, and studies using Trp gene knock-out mice reveal a critical role for TRPM4 in mast cell activation and for mast cell mediated cutaneous anaphylaxis, whereas a direct role of cold- and menthol-activated TRPM8 channels seems to be unlikely for the development of cold urticaria at least in mice.
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