Muscular dystrophy is generally caused by disruptions in the dystrophin glycoprotein complex (DGC) in the membrane of myotubes. In limb-girdle muscular dystrophy, the DGC protein γ-sarcoglycan is deficient. The functions of γ-sarcoglycan in normal myotubes are largely unknown but, on , Dennis Discher and co-workers report that γ-sarcoglycan moderates contractile prestress in skeletal muscle. The authors show first that apoptosis is increased in vitro more than tenfold in γ-sarcoglycan–/– myotubes compared with normal myotubes. Then they use micromanipulation techniques to reveal that, although the γ-sarcoglycan-deficient myotubes are hypercontractile (an observation confirmed by the finding that actomyosin striations are more prominent in the deficient myotubes), their cell adhesion properties are not changed. Finally, the authors report that the phosphorylation of many signaling proteins, in particular those of the MAP kinase pathway, differs between the two cell types. They propose that γ-sarcoglycan is part of a signalling cascade that controls the rate of sarcomerogenesis and/or apoptosis of myotubes; their model may provide hints at ways to treat limb-girdle muscular dystrophy.
