期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：31
页码：12573-12579
DOI：10.1073/pnas.0906545106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 Largemyd 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 Largemyd 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.
