Basal lamina strengthens cell membrane integrity via the laminin G domain-binding motif of [alpha]-dystroglycan

Skeletal muscle basal lamina is linked to the sarcolemma through transmembrane receptors, including integrins and dystroglycan. The function of dystroglycan relies critically on posttranslational glycosylation, a common target shared by a genetically heterogeneous group of muscular dystrophies characterized by [alpha]-dystroglycan hypoglycosylation. Here we show that both dystroglycan and integrin [alpha]7 contribute to force-production of muscles, but that only disruption of dystroglycan causes detachment of the basal lamina from the sarcolemma and renders muscle prone to contraction-induced injury. These phenotypes of dystroglycan-null muscles are recapitulated by [Large.sup.myd] muscles, which have an intact dystrophin-glycoprotein complex and lack only the laminin globular domain-binding motif on [alpha]-dystroglycan. Compromised sarcolemmal integrity is directly shown in [Large.sup.myd] muscles and similarly in normal muscles when arenaviruses compete with matrix proteins for binding [alpha]-dystroglycan. These data provide direct mechanistic insight into how the dystroglycan-linked basal lamina contributes to the maintenance of sarcolemmal integrity and protects muscles from damage. dystroglycanopathy | glycosylation | integrin | membrane damage | muscular dystrophy