The alpha 7 beta 1 integrin in muscle development and disease

The alpha 7 beta 1 integrin is a laminin receptor on the surface of skeleta l myoblasts and myofibers, Alternative forms of both the alpha 7 and beta 1 chains are expressed in a developmentally regulated fashion during myogene sis. These different alpha 7 beta 1 isoforms localize at specific sites on myofibers and appear to have distinct functions in skeletal muscle. These f unctions include the migration and proliferation of developing myoblasts, t he formation and integrity of neuromuscular and myotendinous junctions, and the "gluing" together of muscle fibers that is essential to the generation of contractile force. The alpha 7 beta 1 integrin appears to be both direc tly and indirectly causally related to several muscle diseases. Enhanced ex pression of alpha 7 beta 1-mediated linkage of the extracellular matrix is seen in Duchenne muscular dystrophy and may compensate for the absence of t he dystrophin-mediated linkage. Downregulation of expression of the integri n may contribute to the development of pathology in congenital laminin defi ciencies. Mutations in the alpha 7 integrin gene underlie additional congen ital muscle diseases. The functional roles of this integrin in the formatio n and stability of the neuromuscular and myotendinous junctions and its loc alization between fibers suggest that altered expression or function of thi s integrin may have widespread involvement in other myopathies. The localiz ation of the alpha 7 gene at human chromosome 12q13 is a useful clue for fo cusing such studies.