Expression of γ-Sarcoglycan in Smooth Muscle and Its Interaction with the Smooth Muscle Sarcoglycan-Sarcospan Complex*

The sarcoglycan complex in striated muscle is a heterotetrameric unit integrally associated with sarcospan in the dystrophin-glycoprotein complex. The sarcoglycans, α, β, γ, and δ, 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 β- and δ-sarcoglycans are associated with ε-sarcoglycan, a glycoprotein homologous to α-sarcoglycan. Here, we demonstrate that γ-sarcoglycan is also a component of the sarcoglycan complex in the smooth muscle. First, we show the presence of γ-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 γ-sarcoglycan in smooth muscle was confirmed by analysis of smooth muscle cells in culture. Next, we provide evidence for the association of γ-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 γ-sarcoglycanopathy. Taken together, our results prove that the sarcoglycan complex in vascular and visceral smooth muscle consists of ε-, β-, γ-, and δ-sarcoglycans and is associated with sarcospan.

[1]  H. Sweeney,et al.  Differential requirement for individual sarcoglycans and dystrophin in the assembly and function of the dystrophin-glycoprotein complex. , 2000, Journal of cell science.

[2]  K. Campbell,et al.  Sarcospan-Deficient Mice Maintain Normal Muscle Function , 2000, Molecular and Cellular Biology.

[3]  T. Negri,et al.  Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by β sarcoglycan mutations , 2000, Journal of medical genetics.

[4]  E. Engvall,et al.  Sarcoglycan Isoforms in Skeletal Muscle* , 1999, The Journal of Biological Chemistry.

[5]  E. Mercuri,et al.  Cardiomyopathy in Duchenne, Becker, and sarcoglycanopathies: A role for coronary dysfunction? , 1999, Muscle & nerve.

[6]  K. Campbell,et al.  Dystroglycan inside and out. , 1999, Current opinion in cell biology.

[7]  J. Sanes,et al.  ε-Sarcoglycan Replaces α-Sarcoglycan in Smooth Muscle to Form a Unique Dystrophin-Glycoprotein Complex* , 1999, The Journal of Biological Chemistry.

[8]  K. Campbell,et al.  Biochemical Characterization of the Epithelial Dystroglycan Complex* , 1999, The Journal of Biological Chemistry.

[9]  H. Hama,et al.  Loss of the sarcoglycan complex and sarcospan leads to muscular dystrophy in beta-sarcoglycan-deficient mice. , 1999, Human molecular genetics.

[10]  K. Campbell,et al.  Disruption of the Sarcoglycan–Sarcospan Complex in Vascular Smooth Muscle A Novel Mechanism for Cardiomyopathy and Muscular Dystrophy , 1999, Cell.

[11]  Harry Hines Boulevard,et al.  Role for α-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies , 1999, Nature Cell Biology.

[12]  J. Sanes,et al.  Membrane Targeting and Stabilization of Sarcospan Is Mediated by the Sarcoglycan Subcomplex , 1999, The Journal of cell biology.

[13]  D. Biral,et al.  Ecto-ATPase Activity of α-Sarcoglycan (Adhalin)* , 1999, The Journal of Biological Chemistry.

[14]  A. Sakamoto,et al.  Delineation of genomic deletion in cardiomyopathic hamster , 1999, FEBS letters.

[15]  R. Timpl,et al.  Binding of the G domains of laminin α1 and α2 chains and perlecan to heparin, sulfatides, α‐dystroglycan and several extracellular matrix proteins , 1999 .

[16]  K. Campbell,et al.  Assembly of the Sarcoglycan Complex , 1998, The Journal of Biological Chemistry.

[17]  M. Passos-Bueno,et al.  A first missense mutation in the delta sarcoglycan gene associated with a severe phenotype and frequency of limb-girdle muscular dystrophy type 2F (LGMD2F) in Brazilian sarcoglycanopathies. , 1998, Journal of medical genetics.

[18]  K. Campbell,et al.  The sarcoglycan complex in limb-girdle muscular dystrophy. , 1998, Current opinion in neurology.

[19]  John A. Faulkner,et al.  Progressive Muscular Dystrophy in α-Sarcoglycan–deficient Mice , 1998, The Journal of cell biology.

[20]  R. Wollmann,et al.  γ-Sarcoglycan Deficiency Leads to Muscle Membrane Defects and Apoptosis Independent of Dystrophin , 1998, The Journal of cell biology.

[21]  K. Campbell,et al.  Functional rescue of the sarcoglycan complex in the BIO 14.6 hamster using delta-sarcoglycan gene transfer. , 1998, Molecular cell.

[22]  S. Noguchi,et al.  From dystrophinopathy to sarcoglycanopathy: Evolution of a concept of muscular dystrophy , 1998, Muscle & nerve.

[23]  L. Kunkel,et al.  Human ϵ‐sarcoglycan is highly related to α‐sarcoglycan (adhalin), the limb girdle muscular dystrophy 2D gene 1 , 1998, FEBS letters.

[24]  P. Jongen,et al.  The heart in limb girdle muscular dystrophy , 1998, Heart.

[25]  J. Sanes,et al.  ε-Sarcoglycan, a Broadly Expressed Homologue of the Gene Mutated in Limb-Girdle Muscular Dystrophy 2D* , 1997, The Journal of Biological Chemistry.

[26]  K. Campbell,et al.  Sarcospan, the 25-kDa Transmembrane Component of the Dystrophin-Glycoprotein Complex* , 1997, The Journal of Biological Chemistry.

[27]  Y. Murakami,et al.  Both hypertrophic and dilated cardiomyopathies are caused by mutation of the same gene, delta-sarcoglycan, in hamster: an animal model of disrupted dystrophin-associated glycoprotein complex. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Y. Hayashizaki,et al.  Identification of the Syrian hamster cardiomyopathy gene. , 1997, Human molecular genetics.

[29]  K. Campbell,et al.  Muscular dystrophies and the dystrophin-glycoprotein complex. , 1997, Current opinion in neurology.

[30]  J. McPherson,et al.  Characterization of δ-Sarcoglycan, a Novel Component of the Oligomeric Sarcoglycan Complex Involved in Limb-Girdle Muscular Dystrophy* , 1996, The Journal of Biological Chemistry.

[31]  M. Passos-Bueno,et al.  Autosomal recessive limbgirdle muscular dystrophy, LGMD2F, is caused by a mutation in the δ–sarcoglycan gene , 1996, Nature Genetics.

[32]  K. Campbell,et al.  Dystroglycan: an extracellular matrix receptor linked to the cytoskeleton. , 1996, Current opinion in cell biology.

[33]  J. Stull,et al.  Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[34]  G. Viglietto,et al.  Identification of a novel sarcoglycan gene at 5q33 encoding a sarcolemmal 35 kDa glycoprotein. , 1996, Human molecular genetics.

[35]  L. Kunkel,et al.  Cloning and characterization of the human homologue of a dystrophin related phosphoprotein found at the Torpedo electric organ post-synaptic membrane. , 1996, Human molecular genetics.

[36]  M. F. Peters,et al.  Isoform Diversity of Dystrobrevin, the Murine 87-kDa Postsynaptic Protein (*) , 1996, The Journal of Biological Chemistry.

[37]  D. Bredt,et al.  Interaction of Nitric Oxide Synthase with the Postsynaptic Density Protein PSD-95 and α1-Syntrophin Mediated by PDZ Domains , 1996, Cell.

[38]  L. Kunkel,et al.  Mutations in the Dystrophin-Associated Protein γ-Sarcoglycan in Chromosome 13 Muscular Dystrophy , 1995, Science.

[39]  L. Kunkel,et al.  β–sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex , 1995, Nature Genetics.

[40]  K. Aldape,et al.  Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy , 1995, Cell.

[41]  J. Beckmann,et al.  Primary adhalinopathy: a common cause of autosomal recessive muscular dystrophy of variable severity , 1995, Nature Genetics.

[42]  J. Lefaucheur,et al.  Phenotype of dystrophinopathy in old MDX mice , 1995, The Anatomical record.

[43]  J. Beckmann,et al.  Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy , 1994, Cell.

[44]  O. Ibraghimov-Beskrovnaya,et al.  Primary structure and muscle-specific expression of the 50-kDa dystrophin-associated glycoprotein (adhalin). , 1993, The Journal of biological chemistry.

[45]  J. Ervasti,et al.  A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin , 1993, The Journal of cell biology.

[46]  H. Sweeney,et al.  Dystrophin protects the sarcolemma from stresses developed during muscle contraction. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[47]  K. Campbell,et al.  Deficiency of the 50K dystrophin-associated glycoprotein in severe childhood autosomal recessive muscular dystrophy , 1992, Nature.

[48]  J. Ervasti,et al.  Dystrophin-related protein is localized to neuromuscular junctions of adult skeletal muscle , 1991, Neuron.

[49]  S. Carpenter,et al.  Dystrophin-deficient mdx muscle fibers are preferentially vulnerable to necrosis induced by experimental lengthening contractions , 1990, Journal of the Neurological Sciences.

[50]  J. Ervasti,et al.  Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle , 1990, Nature.

[51]  K. Campbell,et al.  Disruption of the beta-sarcoglycan gene reveals pathogenetic complexity of limb-girdle muscular dystrophy type 2E. , 2000, Molecular cell.

[52]  I. Nonaka,et al.  Expression of dystrophin-associated protein 35DAG (A4) and 50DAG (A2) is confined to striated muscles. , 1994, Journal of biochemistry.