TRPM7 senses oxidative stress to release Zn2+ from unique intracellular vesicles
TRPM7 senses oxidative stress to release Zn2+ from unique intracellular vesicles
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DOI：
10.1073/pnas.1707380114
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发表时间：
2017-07-25
影响因子：
11.1
通讯作者：
Clapham, David E.
中科院分区：
文献类型：
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作者：
Abiria, Sunday A.;Krapivinsky, Grigory;Clapham, David E.
TRPM7(瞬时受体电位阳离子通道亚家族M成员7)调节基因表达和应激诱导的细胞毒性，在器官发育的早期胚胎发育中是必需的。在这里，我们发现大多数TRPM7定位于丰富的细胞内小泡中。这些小泡(M7v)不同于内小体、溶酶体和其他常见的小泡或细胞器。当胞内锌离子浓度升高时，M7V会在谷胱甘肽丰富的还原管腔中积累锌离子。增加活性氧物种(ROS)的处理会触发依赖于TRPM7的锌离子从小泡中释放，而还原型谷胱甘肽则阻止依赖于TRPM7的胞浆锌离子内流。这些观察结果有力地支持了ROS介导的TRPM7激活在锌离子超载后从细胞内小泡中释放锌离子的观点。像内质网一样，这些小泡是一个分布的二价阳离子吸收和释放系统，但在这种情况下，主要的二价离子是锌离子而不是钙离子。
TRPM7 (transient receptor potential cation channel subfamily M member 7) regulates gene expression and stress-induced cytotoxicity and is required in early embryogenesis through organ development. Here, we show that the majority of TRPM7 is localized in abundant intracellular vesicles. These vesicles (M7Vs) are distinct from endosomes, lysosomes, and other familiar vesicles or organelles. M7Vs accumulate Zn2+ in a glutathione-enriched, reduced lumen when cytosolic Zn2+ concentrations are elevated. Treatments that increase reactive oxygen species (ROS) trigger TRPM7-dependent Zn2+ release from the vesicles, whereas reduced glutathione prevents TRPM7-dependent cytosolic Zn2+ influx. These observations strongly support the notion that ROS-mediated TRPM7 activation releases Zn2+ from intracellular vesicles after Zn2+ overload. Like the endoplasmic reticulum, these vesicles are a distributed system for divalent cation uptake and release, but in this case the primary divalent ion is Zn2+ rather than Ca2+.