Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115.
Department of Cardiology, Boston Children's Hospital, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):E6079-E6088. doi: 10.1073/pnas.1707380114. Epub 2017 Jul 10.
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 Zn in a glutathione-enriched, reduced lumen when cytosolic Zn concentrations are elevated. Treatments that increase reactive oxygen species (ROS) trigger TRPM7-dependent Zn release from the vesicles, whereas reduced glutathione prevents TRPM7-dependent cytosolic Zn influx. These observations strongly support the notion that ROS-mediated TRPM7 activation releases Zn from intracellular vesicles after Zn 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 Zn rather than Ca.
瞬时受体电位阳离子通道亚家族 M 成员 7（TRPM7）调节基因表达和应激诱导的细胞毒性，并通过器官发育在早期胚胎发生中发挥作用。在这里，我们表明大多数 TRPM7 定位于丰富的细胞内囊泡中。这些囊泡（M7V）与内体、溶酶体和其他常见的囊泡或细胞器不同。当细胞质中的 Zn 浓度升高时，M7V 在富含谷胱甘肽、还原腔室中积累 Zn。增加活性氧（ROS）的处理会触发 TRPM7 依赖性 Zn 从囊泡中释放，而还原型谷胱甘肽可防止 TRPM7 依赖性细胞质 Zn 内流。这些观察结果强烈支持 ROS 介导的 TRPM7 激活在 Zn 过载后从细胞内囊泡中释放 Zn 的观点。与内质网一样，这些囊泡是二价阳离子摄取和释放的分布式系统，但在这种情况下，主要的二价离子是 Zn 而不是 Ca。
