Topic
Sarcoglycan
About: Sarcoglycan is a research topic. Over the lifetime, 374 publications have been published within this topic receiving 23890 citations.
Papers published on a yearly basis
Papers
TL;DR: It is demonstrated that dystrophin-deficient muscle fibers of the mdx mouse exhibit an increased susceptibility to contraction-induced sarcolemmal rupture, which strongly support the proposition that the primary function of dyStrophin is to provide mechanical reinforcement to the sarcolemma and thereby protect it from the membrane stresses developed during muscle contraction.
Abstract: The protein dystrophin, normally found on the cytoplasmic surface of skeletal muscle cell membranes, is absent in patients with Duchenne muscular dystrophy as well as mdx (X-linked muscular dystrophy) mice. Although its primary structure has been determined, the precise functional role of dystrophin remains the subject of speculation. In the present study, we demonstrate that dystrophin-deficient muscle fibers of the mdx mouse exhibit an increased susceptibility to contraction-induced sarcolemmal rupture. The level of sarcolemmal damage is directly correlated with the magnitude of mechanical stress placed upon the membrane during contraction rather than the number of activations of the muscle. These findings strongly support the proposition that the primary function of dystrophin is to provide mechanical reinforcement to the sarcolemma and thereby protect it from the membrane stresses developed during muscle contraction. Furthermore, the methodology used in this study should prove useful in assessing the efficacy of dystrophin gene therapy in the mdx mouse.
1,542 citations
TL;DR: The hypothesis that the dramatic reduction in the 156K DAG in Duchenne muscular dystrophy leads to a loss of a linkage between the sarcolemma and extra-cellular matrix and that this may render muscle fibres more susceptible to necrosis is supported.
Abstract: The primary sequence of two components of the dystrophin–glycoprotein complex has been established by complementary DNA cloning. The transmembrane 43K and extracellular 156K dystrophin-associated glycoproteins (DAGs) are encoded by a single messenger RNA and the extracellular 156K DAG binds laminin. Thus, the 156K DAG is a new laminin-binding glycoprotein which may provide a linkage between the sarcolemma and extracellular matrix. These results support the hypothesis that the dramatic reduction in the 156K DAG in Duchenne muscular dystrophy leads to a loss of a linkage between the sarcolemma and extra-cellular matrix and that this may render muscle fibres more susceptible to necrosis.
1,456 citations
TL;DR: The present review focuses on the molecular basis of three muscular dystrophic diseases that may be caused by disruptions in the dystrophin-glycoprotein complex, which normally links the subsarcolemmal cytoskeleton to the extracellular matrix in skeletal muscle.
862 citations
TL;DR: The results indicate that the function of dystrophin could be to link this glycop protein to the underlying cytoskeleton and thus help either to preserve membrane stability or to keep the glycoprotein non-uniformly distributed in the sarcolemma.
Abstract: Duchenne muscular dystrophy (DMD) is caused by a defective gene found on the X-chromosome. Dystrophin is encoded by the DMD gene and represents about 0.002% of total muscle protein. Immunochemical studies have shown that dystrophin is localized to the sarcolemma in normal muscle but is absent in muscle from DMD patients. Many features of the predicted primary structure of dystrophin are shared with membrane cytoskeletal proteins, but the precise function of dystrophin in muscle is unknown. Here we report the first isolation of dystrophin from digitonin-solubilized skeletal muscle membranes using wheat germ agglutinin (WGA)-Sepharose. We find that dystrophin is not a glycoprotein but binds to WGA-Sepharose because of its tight association with a WGA-binding glycoprotein. The association of dystrophin with this glycoprotein is disrupted by agents that dissociate cytoskeletal proteins from membranes. We conclude that dystrophin is linked to an integral membrane glycoprotein in the sarcolemma. Our results indicate that the function of dystrophin could be to link this glycoprotein to the underlying cytoskeleton and thus help either to preserve membrane stability or to keep the glycoprotein non-uniformly distributed in the sarcolemma.
778 citations
TL;DR: In this paper, the authors used wild-type mesoangioblasts, a class of vessel-associated stem cells, to correct morphologically and functionally the dystrophic phenotype of virtually all downstream muscles in adult immunocompetent α-sarcoglycan null mice.
Abstract: Preclinical or clinical trials for muscular dystrophies have met with modest success, mainly because of inefficient delivery of viral vectors or donor cells to dystrophic muscles. We report here that intra-arterial delivery of wild-type mesoangioblasts, a class of vessel-associated stem cells, corrects morphologically and functionally the dystrophic phenotype of virtually all downstream muscles in adult immunocompetent α-sarcoglycan (α-SG) null mice, a model organism for limb-girdle muscular dystrophy. When mesoangioblasts isolated from juvenile dystrophic mice and transduced with a lentiviral vector expressing α-SG were injected into the femoral artery of dystrophic mice, they reconstituted skeletal muscle in a manner similar to that seen in wild-type cells. The success of this protocol was mainly due to widespread distribution of donor stem cells through the capillary network, a distinct advantage of this strategy over previous approaches.
685 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 7 |
| 2020 | 4 |
| 2019 | 8 |
| 2018 | 9 |
| 2017 | 9 |
| 2016 | 11 |