scholarly journals Direct interaction of β-dystroglycan with F-actin

2003 ◽  
Vol 375 (2) ◽  
pp. 329-337 ◽  
Author(s):  
Yun-Ju CHEN ◽  
Heather J. SPENCE ◽  
Jacqueline M. CAMERON ◽  
Thomas JESS ◽  
Jane L. ILSLEY ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Direct Interaction ◽  
Cytoplasmic Tail ◽  
Yeast Two Hybrid ◽  
Glycoprotein Complex ◽  
Biological Studies ◽  
Dystrophin Glycoprotein Complex ◽  
Dystrophin Glycoprotein ◽  
Two Hybrid ◽  
Sarcolemmal Integrity

Dystroglycans are essential transmembrane adhesion receptors for laminin. α-Dystroglycan is a highly glycosylated extracellular protein that interacts with laminin in the extracellular matrix and the transmembrane region of β-dystroglycan. β-Dystroglycan, via its cytoplasmic tail, interacts with dystrophin and utrophin and also with the actin cytoskeleton. As a part of the dystrophin–glycoprotein complex of muscles, dystroglycan is also important in maintaining sarcolemmal integrity. Mutations in dystrophin that lead to Duchenne muscular dystrophy also lead to a loss of dystroglycan from the sarcolemma, and chimaeric mice lacking muscle dystroglycan exhibit a severe muscular dystrophy phenotype. Using yeast two-hybrid analysis and biochemical and cell biological studies, we show, in the present study, that the cytoplasmic tail of β-dystroglycan interacts directly with F-actin and, furthermore, that it bundles actin filaments and induces an aberrant actin phenotype when overexpressed in cells.

scholarly journals Caveolin-3: A Causative Process of Chicken Muscular Dystrophy

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1206
Author(s):  
Tateki Kikuchi
Keyword(s):  
Muscular Dystrophy ◽  
Missense Mutation ◽  
Ubiquitin Ligase ◽  
Core Protein ◽  
Ubiquitin Protein Ligase ◽  
Glycoprotein Complex ◽  
Dystrophin Glycoprotein Complex ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Dystrophin Glycoprotein

The etiology of chicken muscular dystrophy is the synthesis of aberrant WW domain containing E3 ubiquitin-protein ligase 1 (WWP1) protein made by a missense mutation of WWP1 gene. The β-dystroglycan that confers stability to sarcolemma was identified as a substrate of WWP protein, which induces the next molecular collapse. The aberrant WWP1 increases the ubiquitin ligase-mediated ubiquitination following severe degradation of sarcolemmal and cytoplasmic β-dystroglycan, and an erased β-dystroglycan in dystrophic αW fibers will lead to molecular imperfection of the dystrophin-glycoprotein complex (DGC). The DGC is a core protein of costamere that is an essential part of force transduction and protects the muscle fibers from contraction-induced damage. Caveolin-3 (Cav-3) and dystrophin bind competitively to the same site of β-dystroglycan, and excessive Cav-3 on sarcolemma will block the interaction of dystrophin with β-dystroglycan, which is another reason for the disruption of the DGC. It is known that fast-twitch glycolytic fibers are more sensitive and vulnerable to contraction-induced small tears than slow-twitch oxidative fibers under a variety of diseased conditions. Accordingly, the fast glycolytic αW fibers must be easy with rapid damage of sarcolemma corruption seen in chicken muscular dystrophy, but the slow oxidative fibers are able to escape from these damages.

scholarly journals Sarcospan-Deficient Mice Maintain Normal Muscle Function

2000 ◽  
Vol 20 (5) ◽  
pp. 1669-1677 ◽  
Author(s):  
Connie S. Lebakken ◽  
David P. Venzke ◽  
Ronald F. Hrstka ◽  
Christina M. Consolino ◽  
John A. Faulkner ◽  
...  
Keyword(s):  
Muscle Function ◽  
Normal Force ◽  
Membrane Component ◽  
Normal Muscle ◽  
Glycoprotein Complex ◽  
Dystrophin Glycoprotein Complex ◽  
Evans Blue Uptake ◽  
Dystrophin Glycoprotein ◽  
Deficient Mice ◽  
Sarcolemmal Integrity

ABSTRACT Sarcospan is an integral membrane component of the dystrophin-glycoprotein complex (DGC) found at the sarcolemma of striated and smooth muscle. The DGC plays important roles in muscle function and viability as evidenced by defects in components of the DGC, which cause muscular dystrophy. Sarcospan is unique among the components of the complex in that it contains four transmembrane domains with intracellular N- and C-terminal domains and is a member of the tetraspan superfamily of proteins. Sarcospan is tightly linked to the sarcoglycans, and together these proteins form a subcomplex within the DGC. Stable expression of sarcospan at the sarcolemma is dependent upon expression of the sarcoglycans. Here we describe the generation and analysis of mice carrying a null mutation in the Sspngene. Surprisingly, the Sspn-deficient muscle maintains expression of other components of the DGC at the sarcolemma, and no gross histological abnormalities of muscle from the mice are observed. The Sspn-deficient muscle maintains sarcolemmal integrity as determined by serum creatine kinase and Evans blue uptake assays, and the Sspn-deficient muscle maintains normal force and power generation capabilities. These data suggest either that sarcospan is not required for normal DGC function or that theSspn-deficient muscle is compensating for the absence of sarcospan, perhaps by utilizing another protein to carry out its function.

Pharmacological rescue of the dystrophin-glycoprotein complex in Duchenne and Becker skeletal muscle explants by proteasome inhibitor treatment

2006 ◽  
Vol 290 (2) ◽  
pp. C577-C582 ◽  
Author(s):  
Stefania Assereto ◽  
Silvia Stringara ◽  
Federica Sotgia ◽  
Gloria Bonuccelli ◽  
Aldobrando Broccolini ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Proteasome Inhibitor ◽  
Becker Muscular Dystrophy ◽  
Culture Conditions ◽  
Mdx Mouse ◽  
Glycoprotein Complex ◽  
Dystrophin Glycoprotein Complex ◽  
Novel Method ◽  
Dystrophin Glycoprotein

In this report, we have developed a novel method to identify compounds that rescue the dystrophin-glycoprotein complex (DGC) in patients with Duchenne or Becker muscular dystrophy. Briefly, freshly isolated skeletal muscle biopsies (termed skeletal muscle explants) from patients with Duchenne or Becker muscular dystrophy were maintained under defined cell culture conditions for a 24-h period in the absence or presence of a specific candidate compound. Using this approach, we have demonstrated that treatment with a well-characterized proteasome inhibitor, MG-132, is sufficient to rescue the expression of dystrophin, β-dystroglycan, and α-sarcoglycan in skeletal muscle explants from patients with Duchenne or Becker muscular dystrophy. These data are consistent with our previous findings regarding systemic treatment with MG-132 in a dystrophin-deficient mdx mouse model (Bonuccelli G, Sotgia F, Schubert W, Park D, Frank PG, Woodman SE, Insabato L, Cammer M, Minetti C, and Lisanti MP. Am J Pathol 163: 1663–1675, 2003). Our present results may have important new implications for the possible pharmacological treatment of Duchenne or Becker muscular dystrophy in humans.

Abstract 78: Hippo Pathway and Dystrophin Glycoprotein Complex Regulate Cardiomyocyte Proliferation

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Yuka Morikawa ◽  
Todd Heallen ◽  
John Leach ◽  
Yang Xiao ◽  
James Martin
Keyword(s):  
Cell Cycle ◽  
Muscular Dystrophy ◽  
Hippo Pathway ◽  
Myocardial Damage ◽  
Heart Regeneration ◽  
Cardiomyocyte Proliferation ◽  
Glycoprotein Complex ◽  
Dystrophin Glycoprotein Complex ◽  
The Hippo Pathway ◽  
Dystrophin Glycoprotein

Regeneration of mammalian heart is limited due to the extremely low renewal rate of cardiomyocytes and their inability to reenter the cell cycle. The Hippo pathway controls heart size during development and represses postnatal heart regeneration by repressing cardiomyocyte proliferation. Our approach for activating adult heart regeneration is to uncover the mechanisms responsible for repression of cardiomyocyte proliferation. We have previously found that deletion of Salv, a modulator of the Hippo pathway, results in myocardial damage repair in postnatal and adult hearts. Deletion of Salv results in activation of the transcription factor, Yap, which positively regulates cytoskeleton and cell cycle genes. We also found that the components of dystrophin glycoprotein complex (DGC) are the target of Yap and DGC regulates heart regeneration. The dystrophin glycoprotein complex (DGC) is essential for muscle maintenance by anchoring the cytoskeleton and extracellular matrix. Disruption of the DGC results in muscular dystrophies, including Duchenne muscular dystrophy, resulting in both skeletal and cardiac myopathies. To explore the connection between DGC and the Hippo pathway, we conditionally deleted Salv in the mdx background, a mouse model of muscular dystrophy. We found that simultaneous disruption of the DGC and the Hippo pathway leads an increased cardiomyocyte proliferation after heart damage. This is associated with increased activity of Yap, suggesting DGC negatively regulate Yap to repress proliferation. We also found that one of the components DGC, dystroglycan directly binds Yap and anchors to the membrane. Our findings provide new insights into the mechanisms leading to heart repair through proliferation of endogenous cardiomyocytes.

A novel FKRP mutation in congenital muscular dystrophy disrupts the dystrophin glycoprotein complex

2007 ◽  
Vol 17 (4) ◽  
pp. 285-289 ◽  
Author(s):  
Heather MacLeod ◽  
Peter Pytel ◽  
Robert Wollmann ◽  
Ewa Chelmicka-Schorr ◽  
Kenneth Silver ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Congenital Muscular Dystrophy ◽  
Glycoprotein Complex ◽  
Dystrophin Glycoprotein Complex ◽  
Dystrophin Glycoprotein

scholarly journals Several dystrophin-glycoprotein complex members are present in crude surface membranes but they are sodium dodecyl sulphate invisible in KCl-washed microsomes from mdx mouse muscle

2010 ◽  
Vol 15 (1) ◽  
Author(s):  
Stéphanie Daval ◽  
Chantal Rocher ◽  
Yan Cherel ◽  
Elisabeth Rumeur
Keyword(s):  
Muscular Dystrophy ◽  
Core Protein ◽  
Surface Membrane ◽  
Sodium Dodecyl ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Mouse Muscle ◽  
Glycoprotein Complex ◽  
Dystrophin Glycoprotein Complex ◽  
Dystrophin Glycoprotein

AbstractThe dystrophin-glycoprotein complex (DGC) is a large trans-sarcolemmal complex that provides a linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. In skeletal muscle, it consists of the dystroglycan, sarcoglycan and cytoplasmic complexes, with dystrophin forming the core protein. The DGC has been described as being absent or greatly reduced in dystrophin-deficient muscles, and this lack is considered to be involved in the dystrophic phenotype. Such a decrease in the DGC content was observed in dystrophin-deficient muscle from humans with muscular dystrophy and in mice with X-linked muscular dystrophy (mdx mice). These deficits were observed in total muscle homogenates and in partially membrane-purified muscle fractions, the so-called KCl-washed microsomes. Here, we report that most of the proteins of the DGC are actually present at normal levels in the mdx mouse muscle plasma membrane. The proteins are detected in dystrophic animal muscles when the immunoblot assay is performed with crude surface membrane fractions instead of the usually employed KCl-washed microsomes. We propose that these proteins form SDS-insoluble membrane complexes when dystrophin is absent.

scholarly journals Increasing α7β1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

2008 ◽  
Vol 294 (2) ◽  
pp. C627-C640 ◽  
Author(s):  
Jianming Liu ◽  
Dean J. Burkin ◽  
Stephen J. Kaufman
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Muscular Dystrophy ◽  
Expression Profiles ◽  
C2c12 Cells ◽  
Glycoprotein Complex ◽  
Dystrophin Glycoprotein Complex ◽  
Dystrophin Glycoprotein

The dystrophin-glycoprotein complex maintains the integrity of skeletal muscle by associating laminin in the extracellular matrix with the actin cytoskeleton. Several human muscular dystrophies arise from defects in the components of this complex. The α7β1-integrin also binds laminin and links the extracellular matrix with the cytoskeleton. Enhancement of α7-integrin levels alleviates pathology in mdx/utrn−/− mice, a model of Duchenne muscular dystrophy, and thus the integrin may functionally compensate for the absence of dystrophin. To test whether increasing α7-integrin levels affects transcription and cellular functions, we generated α7-integrin-inducible C2C12 cells and transgenic mice that overexpress the integrin in skeletal muscle. C2C12 myoblasts with elevated levels of integrin exhibited increased adhesion to laminin, faster proliferation when serum was limited, resistance to staurosporine-induced apoptosis, and normal differentiation. Transgenic expression of eightfold more integrin in skeletal muscle did not result in notable toxic effects in vivo. Moreover, high levels of α7-integrin in both myoblasts and in skeletal muscle did not disrupt global gene expression profiles. Thus increasing integrin levels can compensate for defects in the extracellular matrix and cytoskeleton linkage caused by compromises in the dystrophin-glycoprotein complex without triggering apparent overt negative side effects. These results support the use of integrin enhancement as a therapy for muscular dystrophy.

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