Ultrastructural localization of adhalin, α‐dystroglycan and merosin in normal and dystrophic muscle

Adhalin and α‐dystroglycan are two components of a complex of proteins that, in conjunction with dystrophin, provide a link between the subsarcolemmal cytoskeleton and the basal lamina of the extracellular matrix of skeletal muscle. In the absence of dystrophin, in Duchenne muscular dystrophy (DMD) and the mdx mouse, levels of adhalin, α‐dystroglycan and other components of the complex, are severely reduced, and it has been speculated that this might be an important factor in precipitating myofibre necrosis. However, there is, as yet, little information on how these proteins interact structurally or functionally. From biochemical data it might be predicted that adhalin and α‐dystroglycan are positioned more peripherally in the muscle cell than dystrophin and more proximal than merosin. Using single and double immunogold labelling we here show that adhalin is localized to the plasma membrane with the majority of the gold probe particles situated on the membrane's outer face, while α‐dystroglycan labelling is seen on material which projects from the outer face and which, in places, forms strands that stretch to the basal lamina. When double labelling of laminin and α‐dystroglycan is carried out, laminin is localized to the proximal face of the basal lamina, facing the α‐dystroglycan. In DMD the labelling of adhalin and α‐dystroglycan is severely reduced quantitatively (although the vestige that remains is positioned normally) but merosin is expressed normally, showing that its incorporation is independent of that of dystrophin and its associated proteins.