MG53 nucleates assembly of cell membrane repair machinery.
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.
Cai
Chuanxi
C
Department of Physiology and Biophysics, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Masumiya
Haruko
H
Weisleder
Noah
N
Matsuda
Noriyuki
N
Nishi
Miyuki
M
Hwang
Moonsun
M
Ko
Jae-Kyun
JK
Lin
Peihui
P
Thornton
Angela
A
Zhao
Xiaoli
X
Pan
Zui
Z
Komazaki
Shinji
S
Brotto
Marco
M
Takeshima
Hiroshi
H
Ma
Jianjie
J
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
D002352:Carrier Proteins; C538824:MG53 protein, mouse; D008565:Membrane Proteins; D009124:Muscle Proteins