Elucidating the role of the TRPM7 alpha-kinase: TRPM7 kinase inactivation leads to magnesium deprivation resistance phenotype in mice.
Elucidating the role of the TRPM7 alpha-kinase: TRPM7 kinase inactivation leads to magnesium deprivation resistance phenotype in mice.
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DOI：
10.1038/srep07599
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发表时间：
2014-12-23
影响因子：
4.6
通讯作者：
Ryazanov AG
中科院分区：
文献类型：
--
作者：
Ryazanova LV;Hu Z;Suzuki S;Chubanov V;Fleig A;Ryazanov AG
TRPM 7是一种不寻常的双功能蛋白，含有共价连接到蛋白激酶结构域的离子通道。TRPM 7参与调节细胞和全身镁稳态。虽然TRPM 7离子通道的生物物理特性及其功能已被较好地表征，但TRPM 7酶活性激酶结构域的功能尚未被理解。为了研究TRPM 7激酶活性的生理作用，我们构建了携带无活性TRPM 7激酶的小鼠。我们发现这些小鼠对饮食镁剥夺有抵抗力，存活时间是野生型小鼠的三倍;它们还显示出化学诱导的过敏反应减少。有趣的是，当喂食常规饮食时，突变小鼠的骨镁含量低于野生型小鼠;与野生型小鼠不同，置于镁耗尽饮食的突变小鼠没有改变其骨镁含量。此外，从TRPM 7激酶死亡的动物中分离的小鼠胚胎成纤维细胞表现出对镁剥夺和氧化应激的抵抗力增加。最后，电生理数据显示，激酶死亡的TRPM 7通道的活性没有显着改变。总之，我们的研究结果表明，TRPM 7激酶是镁状态的传感器，并提供了细胞和系统对镁剥夺的反应的协调。
TRPM7 is an unusual bi-functional protein containing an ion channel covalently linked to a protein kinase domain. TRPM7 is implicated in regulating cellular and systemic magnesium homeostasis. While the biophysical properties of TRPM7 ion channel and its function are relatively well characterized, the function of the TRPM7 enzymatically active kinase domain is not understood yet. To investigate the physiological role of TRPM7 kinase activity, we constructed mice carrying an inactive TRPM7 kinase. We found that these mice were resistant to dietary magnesium deprivation, surviving three times longer than wild type mice; also they displayed decreased chemically induced allergic reaction. Interestingly, mutant mice have lower magnesium bone content compared to wild type mice when fed regular diet; unlike wild type mice, mutant mice placed on magnesium-depleted diet did not alter their bone magnesium content. Furthermore, mouse embryonic fibroblasts isolated from TRPM7 kinase-dead animals exhibited increased resistance to magnesium deprivation and oxidative stress. Finally, electrophysiological data revealed that the activity of the kinase-dead TRPM7 channel was not significantly altered. Together, our results suggest that TRPM7 kinase is a sensor of magnesium status and provides coordination of cellular and systemic responses to magnesium deprivation.
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影响因子：
3.8
作者：
Li, Mingjiang;Jiang, Jianmin;Yue, Lixia
通讯作者：
Yue, Lixia
DOI：
10.1016/0167-4889(91)90025-s
发表时间：
1991-08-13
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FUJISE, H;CRUZ, P;LAUF, PK
通讯作者：
LAUF, PK
影响因子：
4.8
作者：
Chubanov, Vladimir;Schlingmann, Karl P.;Gudermann, Thomas
通讯作者：
Gudermann, Thomas
影响因子：
3.5
作者：
Clark, Kristopher;Middelbeek, Jeroen;van Leeuwen, Frank N.
通讯作者：
van Leeuwen, Frank N.
影响因子：
4.8
作者：
Li, Mingjiang;Du, Jianyang;Yue, Lixia
通讯作者：
Yue, Lixia