TRIC channels are essential for Ca2+ handling in intracellular stores
TRIC channels are essential for Ca2+ handling in intracellular stores
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DOI：
10.1038/nature05928
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发表时间：
2007-07-05
期刊：
影响因子：
64.8
通讯作者：
Takeshima, Hiroshi
中科院分区：
文献类型：
--
作者：
Yazawa, Masayuki;Ferrante, Christopher;Takeshima, Hiroshi
细胞信号传导需要通过 Ca2+ 释放通道从细胞内储存有效动员 Ca2+，以及预测离子穿过肌浆/内质网膜的反向运动，以平衡 Ca2+ 释放产生的瞬时负电位(1-7)。 Ca2+ 释放通道在 15 多年前就被克隆(8,9)，而假定的反离子通道的分子身份仍然未知。在这里，我们报告了两种 TRIC（三聚细胞内阳离子）通道亚型，它们在动物细胞类型的细胞内储存中差异表达。 TRIC 亚型包含三个拟议的跨膜片段，并形成具有子弹状结构的同源三聚体。使用纯化的 TRIC 制剂进行电生理学测量可识别单价阳离子选择性通道。在患有胚胎心力衰竭的 TRIC 敲除小鼠中，突变的心肌细胞在细胞内 Ca2+ 处理方面表现出严重的功能障碍。 TRIC 缺陷的骨骼肌肌浆网表现出 K+ 渗透性降低，以及 Ca2+“火花”信号和电压诱导的 Ca2+ 释放的改变。因此，TRIC 通道可能充当反离子通道，与细胞内储存的 Ca2+ 释放同步发挥作用。
Cell signalling requires efficient Ca2+ mobilization from intracellular stores through Ca2+ release channels, as well as predicted counter-movement of ions across the sarcoplasmic/endoplasmic reticulum membrane to balance the transient negative potential generated by Ca2+ release(1-7). Ca2+ release channels were cloned more than 15 years ago(8,9), whereas the molecular identity of putative counter- ion channels remains unknown. Here we report two TRIC ( trimeric intracellular cation) channel subtypes that are differentially expressed on intracellular stores in animal cell types. TRIC subtypes contain three proposed transmembrane segments, and form homo-trimers with a bullet-like structure. Electrophysiological measurements with purified TRIC preparations identify a monovalent cation-selective channel. In TRIC-knockout mice suffering embryonic cardiac failure, mutant cardiac myocytes show severe dysfunction in intracellular Ca2+ handling. The TRIC-deficient skeletal muscle sarcoplasmic reticulum shows reduced K+ permeability, as well as altered Ca2+ 'spark' signalling and voltage-induced Ca2+ release. Therefore, TRIC channels are likely to act as counter- ion channels that function in synchronization with Ca2+ release from intracellular stores.