Edible Wheat Gluten Films: Influence of the Main Process Variables on Film Properties using Response Surface Methodology

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Utrophin Binds Laterally along Actin Filaments and Can Couple Costameric Actin with Sarcolemma When Overexpressed in Dystrophin-deficient Muscle

Dystrophin is widely thought to mechanically link the cortical cytoskeleton with the muscle sarcolemma. Although the dystrophin homolog utrophin can functionally compensate for dystrophin in mice, recent studies question whether utrophin can bind laterally along actin filaments and anchor filaments to the sarcolemma. Herein, we have expressed full-length recombinant utrophin and show that the purified protein is fully soluble with a native molecular weight and molecular dimensions indicative of monomers. We demonstrate that like dystrophin, utrophin can form an extensive lateral association with actin filaments and protect actin filaments from depolymerization in vitro. However, utrophin binds laterally along actin filaments through contribution of acidic spectrin-like repeats rather than the cluster of basic repeats used by dystrophin. We also show that the defective linkage between costameric actin filaments and the sarcolemma in dystrophin-deficient mdx muscle is rescued by overexpression of utrophin. Our results demonstrate that utrophin and dystrophin are functionally interchangeable actin binding proteins, but that the molecular epitopes important for filament binding differ between the two proteins. More generally, our results raise the possibility that spectrin-like repeats may enable some members of the plakin family of cytolinkers to laterally bind and stabilize actin filaments

Other model organisms for sarcomeric muscle diseases.

International audienceModel organisms are vital to our understanding of human muscle biology and disease. The potential of the nematode Caenorhabditis elegans, the fruitfly, Drosophila melanogaster and the zebrafish, Danio rerio, as model genetic organisms for the study of human muscle disease is discussed by examining their muscle biology, muscle genetics and development. The powerful genetic tools available with each organism are outlined. It is concluded that these organisms have already demonstrated potential in facilitating the study of muscle disease and in screening for therapeutic agents