title: MG53 nucleates assembly of cell membrane repair machinery.
abstract: Dynamic membrane repair and remodelling is an elemental process that maintains cell integrity and mediates efficient cellular function. Here we report that MG53, a muscle-specific tripartite motif family protein (TRIM72), is a component of the sarcolemmal membrane-repair machinery. MG53 interacts with phosphatidylserine to associate with intracellular vesicles that traffic to and fuse with sarcolemmal membranes. Mice null for MG53 show progressive myopathy and reduced exercise capability, associated with defective membrane-repair capacity. Injury of the sarcolemmal membrane leads to entry of the extracellular oxidative environment and MG53 oligomerization, resulting in recruitment of MG53-containing vesicles to the injury site. After vesicle translocation, entry of extracellular Ca(2+) facilitates vesicle fusion to reseal the membrane. Our data indicate that intracellular vesicle translocation and Ca(2+)-dependent membrane fusion are distinct steps involved in the repair of membrane damage and that MG53 may initiate the assembly of the membrane repair machinery in an oxidation-dependent manner.
authors.affiliation: Department of Physiology and Biophysics, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
authors.forename: Chuanxi
authors.initials: C
authors.lastname: Cai
authors.forename: Haruko
authors.initials: H
authors.lastname: Masumiya
authors.forename: Noah
authors.initials: N
authors.lastname: Weisleder
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Matsuda
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishi
authors.forename: Moonsun
authors.initials: M
authors.lastname: Hwang
authors.forename: Jae-Kyun
authors.initials: JK
authors.lastname: Ko
authors.forename: Peihui
authors.initials: P
authors.lastname: Lin
authors.forename: Angela
authors.initials: A
authors.lastname: Thornton
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhao
authors.forename: Zui
authors.initials: Z
authors.lastname: Pan
authors.forename: Shinji
authors.initials: S
authors.lastname: Komazaki
authors.forename: Marco
authors.initials: M
authors.lastname: Brotto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D045604:Extracellular Fluid / Q000378:metabolism; D008297:Male; D008561:Membrane Fusion / Q000502:physiology; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D012508:Sarcolemma / Q000378:metabolism* / Q000648:ultrastructure; D022161:Transport Vesicles / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D002352:Carrier Proteins; C538824:MG53 protein, mouse; D008565:Membrane Proteins; D009124:Muscle Proteins