Bidirectional Signaling between Sarcoglycans and the Integrin Adhesion System in Cultured L6 Myocytes

Abstract

The rat L6 skeletal muscle cell line was used to study expression of the dystrophin-containing glycoprotein complex and its interaction with the integrin system involved in the cell-matrix adhesion reaction. A complex of dystrophin and its associated proteins was fully expressed in L6 myotubes, from which anti-dystrophin or anti-␣-sarcoglycan co-precipitated integrin ␣ 5 ␤ 1 and other focal adhesion-associated proteins vinculin, talin, paxillin, and focal adhesion kinase. Immunostaining and confocal microscopy revealed that dystrophin, ␣-sarcoglycan, integrin ␣ 5 ␤ 1 , and vinculin exhibited overlapping distribution in the sarcolemma, especially at focal adhesion-like, spotty structures. Adhesion of cells to fibronectin-or collagen type I-coated dishes resulted in induction of tyrosine phosphorylation of ␣-and ␥-sarcoglycans but not ␤-sarcoglycan. The same proteins were also tyrosine-phosphorylated when L6 cells in suspension were exposed to Arg-Gly-Asp-Ser peptide. All of these tyrosine phosphorylations were inhibited by herbimycin A. On the other hand, treatment of L6 myotubes with ␣-and ␥-sarcoglycan antisense oligodeoxynucleotides resulted in complete disappearance of ␣-and ␥-sarcoglycans and in significant reduction of levels of the associated focal adhesion proteins, which caused about 50% reduction of cell adhesion. These results indicate the existence of bidirectional communication between the dystrophin-containing complex and the integrin adhesion system in cultured L6 myocytes.

Caveolin-3 Knock-out Mice Develop a Progressive Cardiomyopathy and Show Hyperactivation of the p42/44 MAPK Cascade

“…It has been proposed that ␣-dystroglycan, as well the ␤-, ␦-, and ␥-sarcoglycans, may possess a receptor function, whereas ␣-sarcoglycan acts as a downstream effector (37,52). In addition, ␤-dystroglycan and the ␣-and ␥-sarcoglycans have been shown to be tyrosine-phosphorylated upon stimulation with different ligands, implicating them as signaltransducing molecules (35,53). Specifically, ␣-sarcoglycan may function in bi-directional signaling in concert with the integrinadhesion system as well as possess ecto-ATPase activity (35,36).…”

“…In addition, ␤-dystroglycan and the ␣-and ␥-sarcoglycans have been shown to be tyrosine-phosphorylated upon stimulation with different ligands, implicating them as signaltransducing molecules (35,53). Specifically, ␣-sarcoglycan may function in bi-directional signaling in concert with the integrinadhesion system as well as possess ecto-ATPase activity (35,36).…”

“…In this regard, ␣-sarcoglycan is the best-studied member of the DG complex that has been implicated in signaling (35)(36)(37)(38). Thus, we further examined the expression and membrane localization of ␣-sarcoglycan, as a biochemical marker for the DG complex.…”

Cooperation between Thrombospondin-1 Type 1 Repeat Peptides and αvβ3 Integrin Ligands to Promote Melanoma Cell Spreading and Focal Adhesion Kinase Phosphorylation

“…A similar mechanism for cooperation between integrins and proteoglycans has been proposed to promote interactions of melanoma cells with both fibronectin and type IV collagen (45,46). Although some of these effects of proteoglycan binding may require only extracellular interactions, studies in melanoma (43,45,46) and other cell types (47) suggest that cell surface proteoglycans can also induce intracellular signals that modulate integrin function. Protein kinase C is implicated in signaling through syndecan 4 (48), regulates stimulation of melanoma cell chemotaxis by TSP1 (20), and can increase integrin activation (reviewed in Ref.…”

S151A δ-sarcoglycan mutation causes a mild phenotype of cardiomyopathy in mice

“…In cardiac and skeletal muscle, the DGC complex is primarily composed of the four components a-, b-, g-and d-sarcoglycan, essentially involved in sarcolemmal integrity by interaction with integrins that mediates cell adhesion to the extracellular matrix. 3 A discussed association of dystrobrevin and the syntrophins with nNOS suggests that the sarcoglycan complex is involved in signal transduction. 4 Mutations in the a-, b-, g-and d-sarcoglycan genes (Sgca, b, g and d) cause a heterogenous group of autosomal recessive limb girdle muscular dystrophies (LGMD2C-F) clinically characterized by progressive muscle weakness.…”