Zinc Binding to MG53 Facilitates Repair of Injury to Cell Membrane [Molecular Biophysics]

April 13th, 2015 by Cai, C., Lin, P., Zhu, H., Ko, J.-K., Hwang, M., Tan, T., Pan, Z., Korichneva, I., Ma, J.

Zinc (Zn) is an essential trace element that participates in a wide range of biological functions, including wound healing. 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 tripartite motif (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.