title: Zinc Binding to MG53 Protein Facilitates Repair of Injury to Cell Membranes.
abstract: 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.
authors: 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.
authors: Chuanxi
authors: C
authors: Cai
authors: From the Department of Physiology and Biophysics, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, the Department of Surgery.
authors: Peihui
authors: P
authors: Lin
authors: From the Department of Physiology and Biophysics, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, the Department of Surgery.
authors: Hua
authors: H
authors: Zhu
authors: From the Department of Physiology and Biophysics, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854.
authors: Jae-Kyun
authors: JK
authors: Ko
authors: From the Department of Physiology and Biophysics, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854.
authors: Moonsun
authors: M
authors: Hwang
authors: the Department of Surgery.
authors: Tao
authors: T
authors: Tan
authors: Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, and.
authors: Zui
authors: Z
authors: Pan
authors: the Laboratory of Cellular and Molecular Physiology, Department of Sciences, University of Picardie, Amiens 80000, France irina.korichneva@u-picardie.fr.
authors: Irina
authors: I
authors: Korichneva
authors: From the Department of Physiology and Biophysics, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, the Department of Surgery, jianjie.ma@osumc.edu.
authors: Jianjie
authors: J
authors: Ma
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004260:DNA Repair; D004566:Electrodes; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation; D010084:Oxidation-Reduction; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D044968:Regenerative Medicine; D015398:Signal Transduction; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014945:Wound Healing; D015032:Zinc / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C538824:MG53 protein, mouse; D008565:Membrane Proteins; D011994:Recombinant Proteins; C558399:TRIM72 protein, human; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D015032:Zinc
keywords: E3 ubiquitin ligase; redox regulation; signaling; trafficking; vesicles