期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 31, 页码 12573-12579出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0906545106
关键词
dystroglycanopathy; glycosylation; integrin; membrane damage; muscular dystrophy
资金
- Paul D. Wellstone Muscular Dystrophy Cooperative Research Center [1U54NS053672]
- Muscular Dystrophy Association [MDA3936]
- Muscular Dystrophy Association Development
- Welcome Trust [060549]
- U.S. Department of Defense [W81XWH-05-1-0079]
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(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.
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