MG53 nucleates assembly of cell membrane repair machinery
- 30 November 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 11 (1), 56-64
- https://doi.org/10.1038/ncb1812
Abstract
A phosphatidylserine-binding protein, MG53, is shown to participate in membrane repair. MG53 recruits vesicles to the repair site in an oxidation dependent manner and MG53-null mice develop progressive myopathy associated with defective membrane repair. 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 Ca2+ facilitates vesicle fusion to reseal the membrane. Our data indicate that intracellular vesicle translocation and Ca2+-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.Keywords
This publication has 38 references indexed in Scilit:
- Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophyNature Medicine, 2008
- Immuno-proteomic approach to excitation–contraction coupling in skeletal and cardiac muscle: Molecular insights revealed by the mitsuguminsCell Calcium, 2008
- Dysferlin and muscle membrane repairCurrent Opinion in Cell Biology, 2007
- Ca 2+ sparks operated by membrane depolarization require isoform 3 ryanodine receptor channels in skeletal muscleProceedings of the National Academy of Sciences of the United States of America, 2007
- Muscle aging is associated with compromised Ca2+ spark signaling and segregated intracellular Ca2+ releaseThe Journal of cell biology, 2006
- Brain Response to Injury and Neurodegeneration: Endogenous Neuroprotective SignalingAnnals of the New York Academy of Sciences, 2005
- Dysferlin and the plasma membrane repair in muscular dystrophyTrends in Cell Biology, 2004
- The endomembrane requirement for cell surface repairProceedings of the National Academy of Sciences of the United States of America, 2003
- Vesicle accumulation and exocytosis at sites of plasma membrane disruption.The Journal of cell biology, 1995
- Cell Membrane Resealing by a Vesicular Mechanism Similar to Neurotransmitter ReleaseScience, 1994