title: Polymerase transcriptase release factor (PTRF) anchors MG53 protein to cell injury site for initiation of membrane repair.
abstract: Plasma membrane repair is an essential process for maintenance of homeostasis at the cellular and tissue levels, whereas compromised repair capacity contributes to degenerative human diseases. Our recent studies show that MG53 is essential for muscle membrane repair, and defects in MG53 function are linked to muscular dystrophy and cardiac dysfunction. Here we report that polymerase I and transcript release factor (PTRF), a gene known to regulate caveolae membrane structure, is an indispensable component of the membrane repair machinery. PTRF acts as a docking protein for MG53 during membrane repair potentially by binding exposed membrane cholesterol at the injury site. Cells lacking expression of endogenous PTRF show defective trafficking of MG53 to membrane injury sites. A mutation in PTRF associated with human disease results in aberrant nuclear localization of PTRF and disrupts MG53 function in membrane resealing. Although RNAi silencing of PTRF leads to defective muscle membrane repair, overexpression of PTRF can rescue membrane repair defects in dystrophic muscle. Our data suggest that membrane-delimited interaction between MG53 and PTRF contributes to initiation of cell membrane repair, which can be an attractive target for treatment or prevention of tissue injury in human diseases.
authors.affiliation: Department of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Peihui
authors.initials: P
authors.lastname: Lin
authors.forename: Gejing
authors.initials: G
authors.lastname: De
authors.forename: Kyoung-han
authors.initials: KH
authors.lastname: Choi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
authors.forename: Noah
authors.initials: N
authors.lastname: Weisleder
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006367:HeLa Cells; D006331:Heart Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D056945:Hep G2 Cells; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009154:Mutation; D021381:Protein Transport / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000070584:Tripartite Motif Proteins
chemical_list: C497835:CAVIN1 protein, human; D002352:Carrier Proteins; C112745:Cavin1 protein, mouse; C538824:MG53 protein, mouse; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; C558399:TRIM72 protein, human; D000070584:Tripartite Motif Proteins