Cleavage of TRPM7 releases the kinase domain from the ion channel and regulates its participation in Fas-induced apoptosis.
Cleavage of TRPM7 releases the kinase domain from the ion channel and regulates its participation in Fas-induced apoptosis.
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DOI：
10.1016/j.devcel.2012.04.006
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发表时间：
2012-06-12
影响因子：
11.8
通讯作者：
Clapham, David E.
中科院分区：
文献类型：
--
作者：
Desai, Bimal N.;Krapivinsky, Grigory;Navarro, Betsy;Krapivinsky, Luba;Carter, Brett C.;Febvay, Sebastien;Delling, Markus;Penumaka, Anirudh;Ramsey, I. Scott;Manasian, Yunona;Clapham, David E.
瞬时受体电位Melastin-like 7（TRPM 7）是一种通道蛋白，也含有一个调节丝氨酸-苏氨酸激酶结构域。在这里，我们发现Trpm 7 −/− T细胞缺乏Fas受体诱导的凋亡; TRPM 7通道活性参与凋亡过程，并受半胱天冬酶依赖性切割的调节。TRPM 7的这种功能依赖于其作为通道而不是激酶的功能。TRPM 7在D1510处被半胱天冬酶切割，使羧基末端激酶结构域与孔分离，而不破坏释放的激酶的磷酸转移酶活性，但显著增加TRPM 7离子通道活性。此外，我们表明TRPM 7调节受体刺激后Fas受体的内吞区室化，这是通过Fas受体进行细胞凋亡信号传导的重要过程。这些发现提出了这样一种可能性，即TRP通道超家族的其他成员也受到半胱天冬酶介导的切割的调节，对细胞死亡和分化具有广泛的影响。
Transient Receptor Potential Melastatin-like 7 (TRPM7) is a channel protein that also contains a regulatory serine-threonine kinase domain. Here, we find that Trpm7−/− T-cells are deficient in Fas-receptor induced apoptosis; TRPM7 channel activity participates in the apoptotic process and is regulated by caspase-dependent cleavage. This function of TRPM7 is dependent on its function as a channel, but not as a kinase. TRPM7 is cleaved by caspases at D1510, disassociating the carboxy-terminal kinase domain from the pore without disrupting the phosphotransferase activity of the released kinase, but substantially increasing TRPM7 ion channel activity. Furthermore, we show that TRPM7 regulates endocytic compartmentalization of the Fas receptor following receptor stimulation, an important process for apoptotic signaling through Fas receptors. These findings raise the possibility that other members of the TRP channel superfamily are also regulated by caspase-mediated cleavage with wide-ranging implications for cell death and differentiation.
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影响因子：
30.5
作者：
通讯作者：
--
TRP通道基因在小鼠中的组织特异性表达及其在三种不同小鼠菌株中的变异。
影响因子：
4.4
作者：
Kunert-Keil, Christiane;Bisping, Frederike;Kruger, Jana;Brinkmeier, Heinrich
通讯作者：
Brinkmeier, Heinrich
影响因子：
64.5
作者：
Mahrus S;Trinidad JC;Barkan DT;Sali A;Burlingame AL;Wells JA
通讯作者：
Wells JA
影响因子：
16
作者：
Hara, Y;Wakamori, M;Mori, Y
通讯作者：
Mori, Y
影响因子：
64.8
作者：
Li, Feng-Yen;Chaigne-Delalande, Benjamin;Kanellopoulou, Chrysi;Davis, Jeremiah C.;Matthews, Helen F.;Douek, Daniel C.;Cohen, Jeffrey I.;Uzel, Gulbu;Su, Helen C.;Lenardo, Michael J.
通讯作者：
Lenardo, Michael J.