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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Basal lamina strengthens cell membrane integrity via the laminin G domain-binding motif of α-dystroglycan
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Basal lamina strengthens cell membrane integrity via the laminin G domain-binding motif of α-dystroglycan

机译:基底层通过α-营养不良聚糖的层粘连蛋白G结构域结合基序增强细胞膜完整性

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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 a-dystro-glycan hypoglycosylation. Here we show that both dystroglycan and integrin α7 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 α-dystroglycan. Compromised sar-colemmal integrity is directly shown in Large~(myd) muscles and similarly in normal muscles when arenaviruses compete with matrix proteins for binding α-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.
机译:骨骼肌基底层通过跨膜受体(包括整联蛋白和营养不良聚糖)与肌膜相连。 dystroglycan的功能严重依赖于翻译后糖基化,这是遗传上异质的一组肌营养不良症的共同靶点,其特征为a-dystro-glycan低糖基化。在这里,我们显示了dystroglycan和整联蛋白α7都有助于肌肉的力量产生,但是仅dystroglycan的破坏会导致肌层的基底层脱离,并使肌肉易于收缩引起的损伤。 dystroglycan-null肌肉的这些表型可以通过大(myd)肌肉来概括,这些肌肉具有完整的dystrophin-糖蛋白复合物,并且仅缺少α-dystroglycan上的层粘连蛋白球状结构域结合基序。当沙粒病毒与基质蛋白竞争结合α-营养不良糖蛋白时,受损的sar-粘膜完整性直接表现在大肌中,而正常肌中也相似。这些数据提供了直接的机械洞察力,以了解与dystroglycan相连的基底层如何有助于维持肌膜完整性并保护肌肉免受损伤。

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  • 作者单位

    Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, Internal Medicine, The University of Iowa, Iowa City, IA 52242;

    Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, Internal Medicine, The University of Iowa, Iowa City, IA 52242;

    Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, Internal Medicine, The University of Iowa, Iowa City, IA 52242;

    Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, Internal Medicine, The University of Iowa, Iowa City, IA 52242;

    Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Ml 48109-0622;

    Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, Internal Medicine, The University of Iowa, Iowa City, IA 52242;

    Texas Scottish Rite Hospital for Children, Dallas, TX 75219;

    Departments of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037;

    Pathology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242;

    Department of Pediatric Neurology, Children's Medical Center, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Institute of Molecular Medicine and Genetics, The Medical College of Georgia, Augusta, GA 30912;

    Department of Cellular Biology and Anatomy, The Medical College of Georgia, Augusta, GA 30912;

    Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, United Kingdom;

    Departments of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037 Departments of Infectiology, The Scripps Research Institute, La Jolla, CA 92037;

    Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-0622 Departments of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-0622;

    Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics, The University of Iowa Carver College of Medicine, 4283 Carver Biomedical Research Building, 285 Newton Road, Iowa City, IA 52242-1101;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    dystroglycanopathy; glycosylation; integrin; membrane damage; muscular dystrophy;

    机译:肌营养不良症;糖基化整合素膜损伤;肌营养不良症;

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