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PMID:19043407

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Citation

Cai, C, Masumiya, H, Weisleder, N, Matsuda, N, Nishi, M, Hwang, M, Ko, JK, Lin, P, Thornton, A, Zhao, X, Pan, Z, Komazaki, S, Brotto, M, Takeshima, H and Ma, J (2009) MG53 nucleates assembly of cell membrane repair machinery. Nat. Cell Biol. 11:56-64

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.

Links

PubMed PMC2990407 Online version:10.1038/ncb1812

Keywords

Animals; Animals, Newborn; Calcium Signaling/physiology; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Line; Cells, Cultured; Extracellular Fluid/metabolism; Male; Membrane Fusion/physiology; Mice; Mice, Knockout; Muscle Fibers, Skeletal/metabolism; Muscle Fibers, Skeletal/ultrastructure; Muscle Proteins/genetics; Muscle Proteins/metabolism; Oxidative Stress/physiology; Protein Transport/physiology; Regeneration/physiology; Sarcolemma/metabolism; Sarcolemma/ultrastructure; Transport Vesicles/metabolism; Transport Vesicles/ultrastructure

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TRI72

involved_in

GO:0007517: muscle organ development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TRI72

involved_in

GO:0003012: muscle system process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TRI72

located_in

GO:0030659: cytoplasmic vesicle membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TRI72

involved_in

GO:0001778: plasma membrane repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TRI72

located_in

GO:0042383: sarcolemma

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TRI72

enables

GO:0001786: phosphatidylserine binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TRI72

involved_in

GO:0051260: protein homooligomerization

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q1XH17

P

Seeded From UniProt

complete


See also

References

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