Disease relevance of Sgcg

• A defect in any one of the four SG members disrupts the entire SG complex (SGC) and causes limb-girdle muscular dystrophy. zeta-SG has been recently found as a transmembrane protein homologous to gamma-SG and delta-SG [1].
• Mice lacking gamma-sarcoglycan develop progressive muscular dystrophy similar to human muscular dystrophy [2].
• Mice with mutations in gamma-sarcoglycan or delta-sarcoglycan develop cardiomyopathy that is characterized by focal regions of tissue damage [3].
• Pathological analysis of muscle hypertrophy and degeneration in muscular dystrophy in gamma-sarcoglycan-deficient mice [4].
• We found that the gamma-sarcoglycan mutation is least severe in the129SV/J (129) strain and most severe on the DBA 2J JAX (DBA) strain using quantitative measures of Evan's blue dye uptake, as a marker of membrane permeability defects, and hydroxyproline content, as a marker of fibrosis [5].

High impact information on Sgcg

• Cardiomyopathy in mice lacking gamma-sarcoglycan or delta-sarcoglycan is characterized by focal damage [6].
• gamma-Sarcoglycan is a transmembrane, dystrophin-associated protein expressed in skeletal and cardiac muscle [7].
• Apoptotic myonuclei were abundant in skeletal muscle lacking gamma-sarcoglycan, suggesting that programmed cell death contributes to myofiber degeneration [7].
• Vital staining with Evans blue dye revealed that muscle lacking gamma-sarcoglycan developed membrane disruptions like those seen in dystrophin-deficient muscle [7].
• We assessed the functional integrity of this mechanical link and found that isolated muscles lacking gamma-sarcoglycan showed normal resistance to mechanical strain induced by eccentric muscle contraction [2].

Biological context of Sgcg

• Reverse transcription (RT)-PCR showed that the expression pattern of the transcript was almost the reciprocal of that of gamma-SG in various mouse tissues and that the zeta-SG transcript was especially abundant in the brain, suggesting that zeta-SG might play a particular role in the central nervous system [1].
• The reduction in mechanically induced ERK1 phosphorylation in gsg(-/-) muscle was not dependent on age or severity of phenotype, because muscle from both young and old (age 20 wk) animals exhibited a reduced response [8].
• To ascertain whether integrin alpha7 upregulation compensates for the loss of the transmembrane sarcoglycan linkage in sarcoglycan-deficient muscle, we generated mice lacking both integrin alpha7 and gamma-sarcoglycan (gxi) [9].
• To evaluate the promoter function of the 5'-flanking sequence of mouse gamma-sarcoglycan (gamma-SG) gene in vivo, we generated transgenic mice harboring this sequence fused with enhanced green fluorescent protein reporter gene [10].
• Gamma-sarcoglycan-null mice expressing this transgene fully restore gamma-sarcoglycan expression [11].

Anatomical context of Sgcg

• Therefore, muscle hypertrophy of the gsg-/- mice may result from an increase of the number of muscle fibers and probable fiber branching and may not be due to the pseudohypertrophy caused by fibrous and fat tissue replacement, as has been long supposed in muscular dystrophy [4].
• Here, we demonstrate that gamma-sarcoglycan is also a component of the sarcoglycan complex in the smooth muscle [12].
• However, the vascular smooth muscle sarcoglycan complex was intact in the coronary arteries of gamma-sarcoglycan hearts with perturbation of the sarcoglycan complex only within the adjacent myocytes [13].
• Confocal microscopy of the tissues in cross-section showed that all sarcoglycans were detected under the sarcolemma in rats and control mice. delta- and gamma-sarcoglycan labeling demonstrated striations in the longitudinal section, suggesting that the proteins were expressed in the sarcoplasmic reticulum (SR) or transverse tubules (T-tubules) [14].
• 35DAG was detected only in striated muscles (quadriceps femoris and cardiac muscles), but not in other tissues examined, including smooth muscle (aorta, uterus), brain, nerve, lung, and liver [15].

Associations of Sgcg with chemical compounds

• To reduce this secondary vasospasm, we treated gamma-sarcoglycan-deficient mice with the calcium channel antagonist verapamil [13].

Physical interactions of Sgcg

• The incorporation of alpha-SG into the sarcoglycan complex occurs at the final stage by interaction with gamma-SG [16].

Regulatory relationships of Sgcg

• To address this issue, we examined alpha-, beta-, delta-, and gamma-sarcoglycan expression in femoral skeletal muscle from control and dystrophin-deficient mice and rats using confocal microscopy and immunoelectron microscopy [14].

Other interactions of Sgcg

• Zeta-sarcoglycan is a functional homologue of gamma-sarcoglycan in the formation of the sarcoglycan complex [1].
• The absence of sarcoglycan leads to alterations of membrane permeability and apoptosis, two shared features of a number of dystrophies. beta-sarcoglycan and delta-sarcoglycan may form the core of the sarcoglycan subcomplex with alpha- and gamma-sarcoglycan less tightly associated to this core [17].
• At rest, both dystrophic strains had significantly higher ERK1 phosphorylation, and gsg(-/-) muscle also had heightened ERK2 phosphorylation compared with wild-type controls [8].
• The functions of gamma-sarcoglycan (gammaSG) in normal myotubes are largely unknown, however gammaSG is known to assemble into a key membrane complex with dystroglycan and its deficiency is one known cause of limb-girdle muscular dystrophy [18].
• Immunoblotting revealed increases in utrophin and gamma-sarcoglycan in the treated muscles [19].

Analytical, diagnostic and therapeutic context of Sgcg

• Immunoprecipitation experiments revealed that gamma-SG was phosphorylated in normal muscle after eccentric contractions, indicating that members of the DGC are modified in response to mechanical perturbation [8].
• In this study, we generated gamma-sarcoglycan-deficient (gsg-/-) mice by gene targeting [4].
• 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 [12].
• Immunoelectron microscopy clarified that delta-sarcoglycan was localized in the terminal cisternae of the SR, while gamma-sarcoglycan was found in the terminal cisternae and longitudinal SR over I-bands but not over A-bands [14].

References