Cai Chuanxi, Lin Peihui, Zhu Hua, Ko Jae-Kyun, Hwang Moonsun, Tan Tao, Pan Zui, Korichneva Irina, Ma Jianjie
From the Department of Physiology and Biophysics, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, the Center for Cardiovascular Sciences, Albany Medical College, Albany, New York 12208.
From the Department of Physiology and Biophysics, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, the Department of Surgery.
J Biol Chem. 2015 May 29;290(22):13830-9. doi: 10.1074/jbc.M114.620690. Epub 2015 Apr 13.
Zinc is an essential trace element that participates in a wide range of biological functions, including wound healing. Although Zn(2+) deficiency has been linked to compromised wound healing and tissue repair in human diseases, the molecular mechanisms underlying Zn(2+)-mediated tissue repair remain unknown. Our previous studies established that MG53, a TRIM (tripartite motif) family protein, is an essential component of the cell membrane repair machinery. Domain homology analysis revealed that MG53 contains two Zn(2+)-binding motifs. Here, we show that Zn(2+) binding to MG53 is indispensable to assembly of the cell membrane repair machinery. Live cell imaging illustrated that Zn(2+) 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(2+) on membrane repair is abolished in mg53(-/-) muscle fibers, suggesting that MG53 functions as a potential target for Zn(2+) during membrane repair. Mutagenesis studies suggested that both RING and B-box motifs of MG53 constitute Zn(2+)-binding domains that contribute to MG53-mediated membrane repair. Overall, this study establishes a base for Zn(2+) interaction with MG53 in protection against injury to the cell membrane.
锌是一种必需的微量元素，参与广泛的生物学功能，包括伤口愈合。尽管锌离子缺乏与人类疾病中受损的伤口愈合和组织修复有关，但锌离子介导组织修复的分子机制仍不清楚。我们之前的研究表明，MG53，一种TRIM（三方基序）家族蛋白，是细胞膜修复机制的重要组成部分。结构域同源性分析显示，MG53含有两个锌离子结合基序。在这里，我们表明锌离子与MG53的结合对于细胞膜修复机制的组装是必不可少的。活细胞成像表明，细胞外空间的锌离子进入对于含MG53的囊泡转运到急性膜损伤部位以形成修复斑块至关重要。在mg53(-/-)肌纤维中，锌离子对膜修复的作用被消除，这表明MG53在膜修复过程中作为锌离子的潜在靶点发挥作用。诱变研究表明，MG53的RING和B-box基序均构成锌离子结合结构域，有助于MG53介导的膜修复。总体而言，本研究为锌离子与MG53相互作用以保护细胞膜免受损伤奠定了基础。
