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- W2078014265 abstract "Dysferlin and MG53 have been implicated as members of the sarcolemma repair machinery. Skeletal muscle fibers isolated from mice lacking expression of one or the other protein display defective membrane repair process following acute injuries. Our previous studies show that MG53 can nucleate the assembly of the membrane repair machinery by facilitating translocation of intracellular vesicles to membrane injury sites. Dysferlin appears to participate in Ca2+-dependent fusion of these vesicles for formation of a repair patch, but dysferlin itself cannot translocate to the injury site in the absence of MG53. To test the complementary function of MG53 and dysferlin in cell membrane repair, we generated a double knockout mouse lacking both MG53 and dysferlin. While serum creatine kinase (CK) levels of dysferlin-/-, mg53-/-, and wild-type mice were not significantly different from each other, CK levels of the mg53-/-dysferlin-/- mice were significantly elevated at resting condition. This suggests a more severe membrane repair defect. Plasma membrane targeted UV-irradiation of isolated skeletal muscle fibers in the presence of a membrane impermeant dye (FM1-43) was used to directly assay membrane repair. This experimental procedure was modified from previously established protocols for a quantitative assessment of the muscle membrane repair capacity. Compared with dysferlin-/- and mg53-/- fibers, significant elevated entry of FM1-43 dye was observed in mg53-/-dysferlin-/- muscle following UV-irradiation. These results suggest that the involvement of these two proteins in the membrane repair mechanism is more complicated than that as two points along a linear pathway. The additive effects of MG53 and dysferlin in muscle membrane repair suggest the possibility that these two proteins may either sense different membrane injury signals, or that they may act at different compartments of the sarcolemma membrane (caveolae or transverse-tubule network)." @default.
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- W2078014265 date "2012-01-01" @default.
- W2078014265 modified "2023-09-28" @default.
- W2078014265 title "Additive Phenotype of MG53 and Dysferlin Deficiencies in Membrane Repair Function of Skeletal Muscle Fibers" @default.
- W2078014265 doi "https://doi.org/10.1016/j.bpj.2011.11.843" @default.
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