Zinc Binding to MG53 Facilitates Repair of Injury to Cell Membrane
Zinc Binding to MG53 Facilitates Repair of Injury to Cell Membrane
复制标题
DOI：
10.1016/j.bpj.2015.11.3146
复制
发表时间：
2016-02
影响因子：
3.4
通讯作者：
P. Lin;Chuanxi Cai;Hua Zhu;J. Ko;Moonsun Hwang;Zui Pan;Tao Tan;D. Yamazaki;H. Takeshima;I. Korichneva;Jianjie Ma
中科院分区：
文献类型：
--
作者：
P. Lin;Chuanxi Cai;Hua Zhu;J. Ko;Moonsun Hwang;Zui Pan;Tao Tan;D. Yamazaki;H. Takeshima;I. Korichneva;Jianjie Ma
虽然锌缺乏与人类疾病中伤口愈合和组织修复的损害有关，但锌介导的组织修复的分子机制仍不清楚。我们以前的研究证实，MG53是一个三段链(Trim)家族蛋白，是细胞膜修复机制的重要组成部分。结构域同源性分析表明，MG53含有两个锌结合基序。在这里，我们证明了锌与MG53的结合是细胞膜修复机制组装所必需的。活体细胞成像显示，从细胞外间隙进入锌是含MG53的囊泡转移到急性膜损伤部位形成修复补丁所必需的。在MG53-/-肌纤维中，锌对膜修复的作用被取消，这表明MG53在膜修复过程中是锌的潜在靶点。诱变研究表明，MG53的环和B盒基序都构成了锌结合结构域，有助于MG53介导的膜修复。总之，本研究为锌与MG53相互作用保护细胞膜的损伤奠定了基础。
While Zn deficiency has been linked to compromised wound healing and tissue repair in human diseases, the molecular mechanisms underlying Zn-mediated tissue repair remain unknown. Our previous studies established that MG53, a tri partite m otif (TRIM) family protein, is an essential component of the cell membrane repair machinery. Domain homology analysis reveals that MG53 contains two Zn-binding motifs. Here we show that Zn-binding to MG53 is indispensible to the assembly of the cell membrane repair machinery. Live cell imaging illustrates that Zn entry from extracellular space is essential for translocation of MG53-containing vesicles to the acute membrane injury sites for formation of a repair patch. The effect of Zn on membrane repair is abolished in the mg53-/-muscle fibers, suggesting that MG53 functions as a potential target for Zn during membrane repair. Mutagenesis studies suggest that both RING and B-box motifs of MG53 constitute Zn-binding domains that contribute to MG53-mediated membrane repair. Overall, this study establishes a base for Zn interaction with MG53 in protection against injury to the cell membrane.