The Experts below are selected from a list of 369 Experts worldwide ranked by ideXlab platform
Kevin P. Campbell - One of the best experts on this subject based on the ideXlab platform.
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Combined deficiency of alpha and Epsilon Sarcoglycan disrupts the cardiac dystrophin complex
Human molecular genetics, 2011Co-Authors: Alessio Lancioni, Ida Luisa Rotundo, Yvonne M. Kobayashi, Luca D'orsi, S. Aurino, Gerardo Nigro, Giulio Piluso, Dario Acampora, Mafalda Cacciottolo, Kevin P. CampbellAbstract:Cardiomyopathy is a puzzling complication in addition to skeletal muscle pathology for patients with mutations in β-, γ- or δ-Sarcoglycan (SG) genes. Patients with mutations in α-SG rarely have associated cardiomyopathy, or their cardiac pathology is very mild. We hypothesize that a fifth SG, e-SG, may compensate for α-SG deficiency in the heart. To investigate the function of e-SG in striated muscle, we generated an Sgce-null mouse and a Sgca-;Sgce-null mouse, which lacks both α- and e-SGs. While Sgce-null mice showed a wild-type phenotype, with no signs of muscular dystrophy or heart disease, the Sgca-;Sgce-null mouse developed a progressive muscular dystrophy and a more anticipated and severe cardiomyopathy. It shows a complete loss of residual SGs and a strong reduction in both dystrophin and dystroglycan. Our data indicate that e-SG is important in preventing cardiomyopathy in α-SG deficiency.
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dystrophin
2011Co-Authors: Alessio Lancioni, Kevin P. Campbell, Ida Luisa Rotundo, S. Aurino, Gerardo Nigro, Giulio Piluso, Dario Acampora, Mafalda Cacciottolo, Yvonne Monique Kobayashi, Vincenzo NigroAbstract:Combined deficiency of alpha and Epsilon Sarcoglycan disrupts the cardia
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Sarcoglycan complex: implications for metabolic defects in muscular dystrophies.
The Journal of biological chemistry, 2009Co-Authors: Séverine Groh, Haihong Zong, Matthew M. Goddeeris, Connie S. Lebakken, David Venzke, Jeffrey E. Pessin, Kevin P. CampbellAbstract:The Sarcoglycans are known as an integral subcomplex of the dystrophin glycoprotein complex, the function of which is best characterized in skeletal muscle in relation to muscular dystrophies. Here we demonstrate that the white adipocytes, which share a common precursor with the myocytes, express a cell-specific Sarcoglycan complex containing beta-, delta-, and Epsilon-Sarcoglycan. In addition, the adipose Sarcoglycan complex associates with sarcospan and laminin binding dystroglycan. Using multiple Sarcoglycan null mouse models, we show that loss of alpha-Sarcoglycan has no consequence on the expression of the adipocyte Sarcoglycan complex. However, loss of beta- or delta-Sarcoglycan leads to a concomitant loss of the Sarcoglycan complex as well as sarcospan and a dramatic reduction in dystroglycan in adipocytes. We further demonstrate that beta-Sarcoglycan null mice, which lack the Sarcoglycan complex in adipose tissue and skeletal muscle, are glucose-intolerant and exhibit whole body insulin resistance specifically due to impaired insulin-stimulated glucose uptake in skeletal muscles. Thus, our data demonstrate a novel function of the Sarcoglycan complex in whole body glucose homeostasis and skeletal muscle metabolism, suggesting that the impairment of the skeletal muscle metabolism influences the pathogenesis of muscular dystrophy.
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Expression of γ-Sarcoglycan in Smooth Muscle and Its Interaction with the Smooth Muscle Sarcoglycan-Sarcospan Complex
The Journal of biological chemistry, 2000Co-Authors: Rita Barresi, Steven A. Moore, Catherine A. Stolle, Jerry R. Mendell, Kevin P. CampbellAbstract:The Sarcoglycan complex in striated muscle is a heterotetrameric unit integrally associated with sarcospan in the dystrophin-glycoprotein complex. The Sarcoglycans, alpha, beta, gamma, and delta, are mutually dependent with regard to their localization at the sarcolemma, and mutations in any of the Sarcoglycan genes lead to limb-girdle muscular dystrophies type 2C-2F. In smooth muscle beta- and delta-Sarcoglycans are associated with Epsilon-Sarcoglycan, a glycoprotein homologous to alpha-Sarcoglycan. Here, we demonstrate that gamma-Sarcoglycan is also a component of the Sarcoglycan complex in the smooth muscle. First, we show the presence of gamma-Sarcoglycan in a number of smooth muscle-containing organs, and we verify the existence of identical transcripts in skeletal and smooth muscle. The specificity of the expression of gamma-Sarcoglycan in smooth muscle was confirmed by analysis of smooth muscle cells in culture. Next, we provide evidence for the association of gamma-Sarcoglycan with the Sarcoglycan-sarcospan complex by biochemical analysis and comparison among animal models for muscular dystrophy. Moreover, we find disruption of the Sarcoglycan complex in the vascular smooth muscle of a patient with gamma-Sarcoglycanopathy. Taken together, our results prove that the Sarcoglycan complex in vascular and visceral smooth muscle consists of Epsilon-, beta-, gamma-, and delta-Sarcoglycans and is associated with sarcospan.
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Epsilon-Sarcoglycan replaces alpha-Sarcoglycan in smooth muscle to form a unique dystrophin-glycoprotein complex.
The Journal of biological chemistry, 1999Co-Authors: Volker Straub, Madeleine Durbeej, Audrey J. Ettinger, David P. Venzke, Susan Cutshall, Joshua R. Sanes, Kevin P. CampbellAbstract:The Sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle Sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that Epsilon-Sarcoglycan is an integral component of the smooth muscle Sarcoglycan complex along with beta- and delta-Sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The delta-Sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle Sarcoglycan complex, whereas the complex was unaffected in alpha-Sarcoglycan null mice in agreement with the finding that alpha-Sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle Sarcoglycan complex, containing Epsilon-Sarcoglycan, was fully restored following intramuscular injection of recombinant delta-Sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the Sarcoglycan complex and show that Epsilon-Sarcoglycan replaces alpha-Sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in Sarcoglycan-deficient patients.
Audrey J. Ettinger - One of the best experts on this subject based on the ideXlab platform.
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Epsilon-Sarcoglycan replaces alpha-Sarcoglycan in smooth muscle to form a unique dystrophin-glycoprotein complex.
The Journal of biological chemistry, 1999Co-Authors: Volker Straub, Madeleine Durbeej, Audrey J. Ettinger, David P. Venzke, Susan Cutshall, Joshua R. Sanes, Kevin P. CampbellAbstract:The Sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle Sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that Epsilon-Sarcoglycan is an integral component of the smooth muscle Sarcoglycan complex along with beta- and delta-Sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The delta-Sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle Sarcoglycan complex, whereas the complex was unaffected in alpha-Sarcoglycan null mice in agreement with the finding that alpha-Sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle Sarcoglycan complex, containing Epsilon-Sarcoglycan, was fully restored following intramuscular injection of recombinant delta-Sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the Sarcoglycan complex and show that Epsilon-Sarcoglycan replaces alpha-Sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in Sarcoglycan-deficient patients.
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Epsilon Sarcoglycan replaces alpha Sarcoglycan in smooth muscle to form a unique dystrophin glycoprotein complex
Journal of Biological Chemistry, 1999Co-Authors: Volker Straub, Madeleine Durbeej, Audrey J. Ettinger, David P. Venzke, Susan Cutshall, Joshua R. Sanes, Kevin P. CampbellAbstract:Abstract The Sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle Sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that e-Sarcoglycan is an integral component of the smooth muscle Sarcoglycan complex along with β- and δ-Sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The δ-Sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle Sarcoglycan complex, whereas the complex was unaffected in α-Sarcoglycan null mice in agreement with the finding that α-Sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle Sarcoglycan complex, containing e-Sarcoglycan, was fully restored following intramuscular injection of recombinant δ-Sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the Sarcoglycan complex and show that e-Sarcoglycan replaces α-Sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in Sarcoglycan-deficient patients.
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Progressive Muscular Dystrophy in α-Sarcoglycan–deficient Mice
The Journal of cell biology, 1998Co-Authors: Franck Duclos, Connie S. Lebakken, David Venzke, Steven A. Moore, Volker Straub, Ron F. Hrstka, Rachelle H. Crosbie, Madeleine Durbeej, Audrey J. Ettinger, Jack H. Van Der MeulenAbstract:Limb-girdle muscular dystrophy type 2D (LGMD 2D) is an autosomal recessive disorder caused by mutations in the alpha-Sarcoglycan gene. To determine how alpha-Sarcoglycan deficiency leads to muscle fiber degeneration, we generated and analyzed alpha-Sarcoglycan- deficient mice. Sgca-null mice developed progressive muscular dystrophy and, in contrast to other animal models for muscular dystrophy, showed ongoing muscle necrosis with age, a hallmark of the human disease. Sgca-null mice also revealed loss of sarcolemmal integrity, elevated serum levels of muscle enzymes, increased muscle masses, and changes in the generation of absolute force. Molecular analysis of Sgca-null mice demonstrated that the absence of alpha-Sarcoglycan resulted in the complete loss of the Sarcoglycan complex, sarcospan, and a disruption of alpha-dystroglycan association with membranes. In contrast, no change in the expression of Epsilon-Sarcoglycan (alpha-Sarcoglycan homologue) was observed. Recombinant alpha-Sarcoglycan adenovirus injection into Sgca-deficient muscles restored the Sarcoglycan complex and sarcospan to the membrane. We propose that the Sarcoglycan-sarcospan complex is requisite for stable association of alpha-dystroglycan with the sarcolemma. The Sgca-deficient mice will be a valuable model for elucidating the pathogenesis of Sarcoglycan deficient limb-girdle muscular dystrophies and for the development of therapeutic strategies for this disease.
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ε-Sarcoglycan, a Broadly Expressed Homologue of the Gene Mutated in Limb-Girdle Muscular Dystrophy 2D
The Journal of biological chemistry, 1997Co-Authors: Audrey J. Ettinger, Guoping Feng, Joshua R. SanesAbstract:The Sarcoglycans are transmembrane components of the dystrophin-glycoprotein complex, which links the cytoskeleton to the extracellular matrix in adult muscle fibers. Mutations in all four known Sarcoglycan genes (alpha, beta, gamma, and delta) have been found in humans with limb-girdle muscular dystrophy. We have identified a novel protein, Epsilon-Sarcoglycan, that shares 44% amino acid identity with alpha-Sarcoglycan (adhalin). We show that Epsilon-Sarcoglycan is a membrane-associated glycoprotein and document its expression by Northern blotting, immunoblotting, and immunofluorescence. In contrast to alpha-delta Sarcoglycans, which are expressed predominantly or exclusively in striated muscle, Epsilon-Sarcoglycan is broadly distributed in muscle and nonmuscle cells of both embryos and adults. These results raise the possibility that Sarcoglycan-containing complexes mediate membrane-matrix interactions in many cell types.
Volker Straub - One of the best experts on this subject based on the ideXlab platform.
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Epsilon Sarcoglycan replaces alpha Sarcoglycan in smooth muscle to form a unique dystrophin glycoprotein complex
Journal of Biological Chemistry, 1999Co-Authors: Volker Straub, Madeleine Durbeej, Audrey J. Ettinger, David P. Venzke, Susan Cutshall, Joshua R. Sanes, Kevin P. CampbellAbstract:Abstract The Sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle Sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that e-Sarcoglycan is an integral component of the smooth muscle Sarcoglycan complex along with β- and δ-Sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The δ-Sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle Sarcoglycan complex, whereas the complex was unaffected in α-Sarcoglycan null mice in agreement with the finding that α-Sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle Sarcoglycan complex, containing e-Sarcoglycan, was fully restored following intramuscular injection of recombinant δ-Sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the Sarcoglycan complex and show that e-Sarcoglycan replaces α-Sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in Sarcoglycan-deficient patients.
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Epsilon-Sarcoglycan replaces alpha-Sarcoglycan in smooth muscle to form a unique dystrophin-glycoprotein complex.
The Journal of biological chemistry, 1999Co-Authors: Volker Straub, Madeleine Durbeej, Audrey J. Ettinger, David P. Venzke, Susan Cutshall, Joshua R. Sanes, Kevin P. CampbellAbstract:The Sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle Sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that Epsilon-Sarcoglycan is an integral component of the smooth muscle Sarcoglycan complex along with beta- and delta-Sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The delta-Sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle Sarcoglycan complex, whereas the complex was unaffected in alpha-Sarcoglycan null mice in agreement with the finding that alpha-Sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle Sarcoglycan complex, containing Epsilon-Sarcoglycan, was fully restored following intramuscular injection of recombinant delta-Sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the Sarcoglycan complex and show that Epsilon-Sarcoglycan replaces alpha-Sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in Sarcoglycan-deficient patients.
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Progressive Muscular Dystrophy in α-Sarcoglycan–deficient Mice
The Journal of cell biology, 1998Co-Authors: Franck Duclos, Connie S. Lebakken, David Venzke, Steven A. Moore, Volker Straub, Ron F. Hrstka, Rachelle H. Crosbie, Madeleine Durbeej, Audrey J. Ettinger, Jack H. Van Der MeulenAbstract:Limb-girdle muscular dystrophy type 2D (LGMD 2D) is an autosomal recessive disorder caused by mutations in the alpha-Sarcoglycan gene. To determine how alpha-Sarcoglycan deficiency leads to muscle fiber degeneration, we generated and analyzed alpha-Sarcoglycan- deficient mice. Sgca-null mice developed progressive muscular dystrophy and, in contrast to other animal models for muscular dystrophy, showed ongoing muscle necrosis with age, a hallmark of the human disease. Sgca-null mice also revealed loss of sarcolemmal integrity, elevated serum levels of muscle enzymes, increased muscle masses, and changes in the generation of absolute force. Molecular analysis of Sgca-null mice demonstrated that the absence of alpha-Sarcoglycan resulted in the complete loss of the Sarcoglycan complex, sarcospan, and a disruption of alpha-dystroglycan association with membranes. In contrast, no change in the expression of Epsilon-Sarcoglycan (alpha-Sarcoglycan homologue) was observed. Recombinant alpha-Sarcoglycan adenovirus injection into Sgca-deficient muscles restored the Sarcoglycan complex and sarcospan to the membrane. We propose that the Sarcoglycan-sarcospan complex is requisite for stable association of alpha-dystroglycan with the sarcolemma. The Sgca-deficient mice will be a valuable model for elucidating the pathogenesis of Sarcoglycan deficient limb-girdle muscular dystrophies and for the development of therapeutic strategies for this disease.
Madeleine Durbeej - One of the best experts on this subject based on the ideXlab platform.
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Epsilon Sarcoglycan replaces alpha Sarcoglycan in smooth muscle to form a unique dystrophin glycoprotein complex
Journal of Biological Chemistry, 1999Co-Authors: Volker Straub, Madeleine Durbeej, Audrey J. Ettinger, David P. Venzke, Susan Cutshall, Joshua R. Sanes, Kevin P. CampbellAbstract:Abstract The Sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle Sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that e-Sarcoglycan is an integral component of the smooth muscle Sarcoglycan complex along with β- and δ-Sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The δ-Sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle Sarcoglycan complex, whereas the complex was unaffected in α-Sarcoglycan null mice in agreement with the finding that α-Sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle Sarcoglycan complex, containing e-Sarcoglycan, was fully restored following intramuscular injection of recombinant δ-Sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the Sarcoglycan complex and show that e-Sarcoglycan replaces α-Sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in Sarcoglycan-deficient patients.
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Epsilon-Sarcoglycan replaces alpha-Sarcoglycan in smooth muscle to form a unique dystrophin-glycoprotein complex.
The Journal of biological chemistry, 1999Co-Authors: Volker Straub, Madeleine Durbeej, Audrey J. Ettinger, David P. Venzke, Susan Cutshall, Joshua R. Sanes, Kevin P. CampbellAbstract:The Sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle Sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that Epsilon-Sarcoglycan is an integral component of the smooth muscle Sarcoglycan complex along with beta- and delta-Sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The delta-Sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle Sarcoglycan complex, whereas the complex was unaffected in alpha-Sarcoglycan null mice in agreement with the finding that alpha-Sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle Sarcoglycan complex, containing Epsilon-Sarcoglycan, was fully restored following intramuscular injection of recombinant delta-Sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the Sarcoglycan complex and show that Epsilon-Sarcoglycan replaces alpha-Sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in Sarcoglycan-deficient patients.
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Progressive Muscular Dystrophy in α-Sarcoglycan–deficient Mice
The Journal of cell biology, 1998Co-Authors: Franck Duclos, Connie S. Lebakken, David Venzke, Steven A. Moore, Volker Straub, Ron F. Hrstka, Rachelle H. Crosbie, Madeleine Durbeej, Audrey J. Ettinger, Jack H. Van Der MeulenAbstract:Limb-girdle muscular dystrophy type 2D (LGMD 2D) is an autosomal recessive disorder caused by mutations in the alpha-Sarcoglycan gene. To determine how alpha-Sarcoglycan deficiency leads to muscle fiber degeneration, we generated and analyzed alpha-Sarcoglycan- deficient mice. Sgca-null mice developed progressive muscular dystrophy and, in contrast to other animal models for muscular dystrophy, showed ongoing muscle necrosis with age, a hallmark of the human disease. Sgca-null mice also revealed loss of sarcolemmal integrity, elevated serum levels of muscle enzymes, increased muscle masses, and changes in the generation of absolute force. Molecular analysis of Sgca-null mice demonstrated that the absence of alpha-Sarcoglycan resulted in the complete loss of the Sarcoglycan complex, sarcospan, and a disruption of alpha-dystroglycan association with membranes. In contrast, no change in the expression of Epsilon-Sarcoglycan (alpha-Sarcoglycan homologue) was observed. Recombinant alpha-Sarcoglycan adenovirus injection into Sgca-deficient muscles restored the Sarcoglycan complex and sarcospan to the membrane. We propose that the Sarcoglycan-sarcospan complex is requisite for stable association of alpha-dystroglycan with the sarcolemma. The Sgca-deficient mice will be a valuable model for elucidating the pathogenesis of Sarcoglycan deficient limb-girdle muscular dystrophies and for the development of therapeutic strategies for this disease.
Joshua R. Sanes - One of the best experts on this subject based on the ideXlab platform.
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Epsilon-Sarcoglycan replaces alpha-Sarcoglycan in smooth muscle to form a unique dystrophin-glycoprotein complex.
The Journal of biological chemistry, 1999Co-Authors: Volker Straub, Madeleine Durbeej, Audrey J. Ettinger, David P. Venzke, Susan Cutshall, Joshua R. Sanes, Kevin P. CampbellAbstract:The Sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle Sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that Epsilon-Sarcoglycan is an integral component of the smooth muscle Sarcoglycan complex along with beta- and delta-Sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The delta-Sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle Sarcoglycan complex, whereas the complex was unaffected in alpha-Sarcoglycan null mice in agreement with the finding that alpha-Sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle Sarcoglycan complex, containing Epsilon-Sarcoglycan, was fully restored following intramuscular injection of recombinant delta-Sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the Sarcoglycan complex and show that Epsilon-Sarcoglycan replaces alpha-Sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in Sarcoglycan-deficient patients.
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Epsilon Sarcoglycan replaces alpha Sarcoglycan in smooth muscle to form a unique dystrophin glycoprotein complex
Journal of Biological Chemistry, 1999Co-Authors: Volker Straub, Madeleine Durbeej, Audrey J. Ettinger, David P. Venzke, Susan Cutshall, Joshua R. Sanes, Kevin P. CampbellAbstract:Abstract The Sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle Sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that e-Sarcoglycan is an integral component of the smooth muscle Sarcoglycan complex along with β- and δ-Sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The δ-Sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle Sarcoglycan complex, whereas the complex was unaffected in α-Sarcoglycan null mice in agreement with the finding that α-Sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle Sarcoglycan complex, containing e-Sarcoglycan, was fully restored following intramuscular injection of recombinant δ-Sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the Sarcoglycan complex and show that e-Sarcoglycan replaces α-Sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in Sarcoglycan-deficient patients.
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ε-Sarcoglycan, a Broadly Expressed Homologue of the Gene Mutated in Limb-Girdle Muscular Dystrophy 2D
The Journal of biological chemistry, 1997Co-Authors: Audrey J. Ettinger, Guoping Feng, Joshua R. SanesAbstract:The Sarcoglycans are transmembrane components of the dystrophin-glycoprotein complex, which links the cytoskeleton to the extracellular matrix in adult muscle fibers. Mutations in all four known Sarcoglycan genes (alpha, beta, gamma, and delta) have been found in humans with limb-girdle muscular dystrophy. We have identified a novel protein, Epsilon-Sarcoglycan, that shares 44% amino acid identity with alpha-Sarcoglycan (adhalin). We show that Epsilon-Sarcoglycan is a membrane-associated glycoprotein and document its expression by Northern blotting, immunoblotting, and immunofluorescence. In contrast to alpha-delta Sarcoglycans, which are expressed predominantly or exclusively in striated muscle, Epsilon-Sarcoglycan is broadly distributed in muscle and nonmuscle cells of both embryos and adults. These results raise the possibility that Sarcoglycan-containing complexes mediate membrane-matrix interactions in many cell types.