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

ABSTRACT: 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 alpha7 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(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(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.

SUBMITTER: Han R

PROVIDER: S-EPMC2715328 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Agrin binds to the nerve-muscle basal lamina via laminin.

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High degree of conservation of the enzymes synthesizing the laminin-binding glycoepitope of α-dystroglycan.

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