Muscular dystrophy is a category of hereditary diseases that are characterized by progressive muscle weakness, muscle degeneration, muscle fibrosis and other associated symptoms such as cardiopulmonary complications and nervous system malfunction. Studies on the genetic and molecular causes of muscular dystrophies reveal that deficiency in dystrophin-glycoprotein complex (DGC) is the key of most types of muscular dystrophy. The DGC consists of two core proteins--a cytoplasmic protein dystrophin (DYS) and a transmembrane protein dystroglycan (DG). On the cytoplasmic side of sarcolemma (muscle cell membrane), DYS binds to F-actin (a component of cytoskeleton underlying the cell membrane) and DG. On the extracellular, DG binds to laminin (LAM), an extracellular matrix protein. Together, these proteins form an axis of F-actin-DYS-DG-LAM from cytoplasm across sarcolemma to extracellular space, linking cytoskeleton to extracellular matrix, which has been proven to play an important structural role in stabilizing sarcolemma and transmitting force across sarcolemma during muscle fiber contraction. Further studies on the function of DG reveal that it also plays an important role in basal membrane assembly, cell signaling and neuromuscular junction formation. Interestingly, these functions are less or not affected by disruption of other components of the DYS-DG-LAM axis, which indicates that there might be "free DG" that works without being incorporated into DGC complex. To test this hypothesis, I used quantitative western blot to quantify the absolute concentration of DYS, DG and LAM in skeletal muscles and found out that the molar stoichiometry of DYS:DG:LAM in skeletal muscle was 1:40:1, indicating a large fraction of DG might not be incorporated in DGC. To further confirm the existence of "free DG," I'm currently using different protein baits to coimmunoprecipitate DGC to find out whether all DG are associated with DGC on sarcolemma.