Disease relevance of Sgca

• 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 [1].
• 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 [1].
• In this report, we utilized recombinant adeno-associated virus containing a U7 cassette carrying an antisense sequence aimed at inducing exon skipping of the dystrophin gene or containing the alpha-sarcoglycan gene to alleviate the dystrophic phenotype of the mdx and Sgca-null mice, respectively [2].

High impact information on Sgca

• Overexpression of epsilon-SG in normal mice resulted in substitution of epsilon-SG for alpha-SG in the SG complex of skeletal muscle without any obvious abnormalities [3].
• The ultrastructural localization of adhalin and its relations to dystrophin, beta-dystroglycan, and beta-spectrin were studied in normal murine skeletal myofibers [4].
• Single-immunolabeling electron microscopy showed that the adhalin was located just inside the muscle plasma membrane or inside the myofiber a short distance from the plasma membrane [4].
• Fusion proteins containing alpha-syntrophin sequences bound not only to dystrophin but also to all three DGC syntrophins, adhalin, and gp35 [5].
• Alpha-sarcoglycan (Sgca) is a transmembrane glycoprotein of the dystrophin complex located at skeletal and cardiac muscle sarcolemma [6].

Chemical compound and disease context of Sgca

• In severe childhood autosomal recessive muscular dystrophy, a selective deficiency of adhalin (50-kd glycoprotein) also causes dysfunction of the dystrophin-glycoprotein complex [7].

Biological context of Sgca

• EDL muscle of Sgca-null mice showed twitch and tetanic kinetics comparable with those of wild-type controls [6].
• Adhalin expression in embryonic mouse muscle was coincident with primary myogenesis [8].
• We conclude that the alpha-SG promoter is activated by MyoD, which interacts with TFIID and TFIIB in a protein complex differentially located at the distal promoter and around the proximal promoter during myogenic cell differentiation [9].

Anatomical context of Sgca

• In contrast to the EDL, soleus muscle of Sgca-null mice contained a higher number of regenerating fibers and thus higher levels of embryonic MHC [6].
• Contrary to EDL fibers, soleus muscle fibers of Sgca-null mice distinctively showed right shift of the pCa-tension (pCa is the negative log of Ca2+ concentration) relationships and reduced sensitivity to caffeine of sarcoplasmic reticulum [6].
• Muscle masses were 40-100% larger for Sgca-null compared with age- and gender-matched wild-type mice, with the majority of the increased muscle mass for Sgca-null mice attributable to greater connective tissue and water contents [10].
• This work describes the culture of Sol8 cell line that expresses neither dystrophin nor adhalin, a dystrophin-associated protein [11].
• Additionally, members of the sarcolemmal dystrophin-glycoprotein complex (i.e., dystrophin, adhalin, beta1-dystroglycan) immunolocalize in the cytosol of differentiating myoblasts, whereas anti-dystrophin and anti-beta1-dystroglycan clearly delineate the sarcolemma in myotubes [12].

Associations of Sgca with chemical compounds

• Furthermore, the diffuse extrajunctional appearance of adhalin, beta-dystroglycan, and AChR was observed after pharmacological denervation through the subcutaneous administration of succinylcholine [13].

Physical interactions of Sgca

• The incorporation of alpha-SG into the sarcoglycan complex occurs at the final stage by interaction with gamma-SG [14].

Regulatory relationships of Sgca

• Adhalin was specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types [8].

Other interactions of Sgca

• Thus, the goal of the present study was to investigate whether overexpression of epsilon-SG can compensate for dysfunction of alpha-SG [3].
• These data suggest that adhalin is highly specific for striated muscle and that it is linked with the formation of a fully functional muscle fiber [8].
• Adhalin, or alpha-sarcoglycan, is a 50-kDa glycoprotein that was originally characterized as a muscle membrane protein [8].
• Chromatin immunoprecipitation assays revealed that MyoD, TFIID, and TFIIB interact with the distal promoter in C2C12 myoblasts, a stage at which the alpha-SG promoter appears to drive basal activity [9].

References