Zinc Binding to MG53 Protein Facilitates Repair of Injury to Cell Membranes

• Published in: The Journal of biological chemistry Vol. 290; no. 22; pp. 13830 - 13839
• Main Authors: Cai, Chuanxi, Lin, Peihui, Zhu, Hua, Ko, Jae-Kyun, Hwang, Moonsun, Tan, Tao, Pan, Zui, Korichneva, Irina, Ma, Jianjie
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.05.2015; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Motifs; Animals; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Biology; Cell Line; Cell Membrane - metabolism; DNA Repair; E3 ubiquitin ligase; Electrodes; Escherichia coli - metabolism; Humans; Life Sciences; Membrane Proteins; Mice; Mice, Transgenic; Microscopy, Confocal; Muscle, Skeletal - metabolism; Mutation; Oxidation-Reduction; Plasmids - metabolism; Protein Binding; Protein Structure, Tertiary; Recombinant Proteins - metabolism; redox regulation; Regenerative Medicine; Signal Transduction; signaling; trafficking; Tripartite Motif Proteins; Ubiquitin-Protein Ligases - metabolism; vesicles; Wound Healing; Zinc - metabolism; E3 ubiquitin ligase; redox regulation; signaling; trafficking; vesicles
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M114.620690

Zinc is an essential trace element that participates in a wide range of biological functions, including wound healing. Although Zn2+ deficiency has been linked to compromised wound healing and tissue repair in human diseases, the molecular mechanisms underlying Zn2+-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 Zn2+-binding motifs. Here, we show that Zn2+ binding to MG53 is indispensable to assembly of the cell membrane repair machinery. Live cell imaging illustrated that Zn2+ 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 Zn2+ on membrane repair is abolished in mg53−/− muscle fibers, suggesting that MG53 functions as a potential target for Zn2+ during membrane repair. Mutagenesis studies suggested that both RING and B-box motifs of MG53 constitute Zn2+-binding domains that contribute to MG53-mediated membrane repair. Overall, this study establishes a base for Zn2+ interaction with MG53 in protection against injury to the cell membrane. Background: MG53, a zinc finger protein, is essential to cell membrane repair. It is not known whether zinc contributes to MG53-mediated membrane repair. Results: Chelation of Zn2+ or mutation of Zn2+-binding motifs in MG53 affects membrane repair. Conclusion: Zn2+ binding to MG53 is required for membrane repair. Significance: This study establishes a base for Zn2+ interaction with MG53 in protection against injury to the cell membrane.