TRPM7 regulates polarized cell movements.
TRPM7 regulates polarized cell movements.
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DOI：
10.1042/bj20101678
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发表时间：
2011-03-15
期刊：
影响因子：
--
通讯作者：
Runnels LW
中科院分区：
文献类型：
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作者：
Su LT;Liu W;Chen HC;González-Pagán O;Habas R;Runnels LW
TRPM7是一种钙离子和镁离子通道，具有自己的激酶域。作为一种激酶，该蛋白与肌动球蛋白收缩能力的控制有关，而该通道已被发现调节细胞黏附和细胞内镁离子的稳态。在这里，我们表明，通过RNA干扰在成纤维细胞中耗尽TRPM7会改变细胞形态、细胞骨架以及细胞形成片状脂膜和执行极化细胞运动的能力。下拉纯化实验表明，TRPM7的敲除可以防止细胞在受到刺激时激活RAC和CDC42，从而迁移到细胞伤口中。TRPM7的重新表达逆转了这些表型变化，出人意料的是，TRPM7的激酶失活突变体的表达也是如此。令人惊讶的是，镁离子转运体SLC41A2的表达也有效地恢复了细胞形态的变化，细胞骨架的破坏，以及由于通道激酶耗尽而导致的定向细胞运动。这些数据揭示了镁离子在TRPM7的S控制细胞骨架及其调节极化细胞运动的能力中扮演的重要角色。
TRPM7 is a Ca2+ and Mg2+ permeant ion channel in possession of its own kinase domain. As a kinase, the protein has been linked to the control of actomyosin contractility, whereas the channel has been found to regulate cell adhesion as well as cellular Mg2+ homeostasis. Here we show that depletion of TRPM7 by RNA interference in fibroblasts alters cell morphology, the cytoskeleton, and the ability of cells to form lamellipodia and to execute polarized cell movements. A pulldown purification assay revealed that knockdown of TRPM7 prevents cells from activating Rac and Cdc42 when stimulated to migrate into a cellular wound. Re-expression of TRPM7 reverses these phenotypic changes, as does, unexpectedly, expression of a kinase-inactive mutant of TRPM7. Surprisingly, expression of the Mg2+ transporter SLC41A2 is also effective restoring the change in cell morphology, disruption of the cytoskeleton, and directional cell motility caused by depletion of the channel-kinase. These data uncover an essential role for Mg2+ in TRPM7's control over the cytoskeleton and its ability to regulate polarized cell movements.