Basal lamina strengthens cell membrane integrity via the laminin G domain-binding motif of α-dystroglycan
| Autor: | John A. Faulkner, Kevin P. Campbell, Stefan Kunz, Ulrike Mayer, Renzhi Han, Motoi Kanagawa, Takako Yoshida-Moriguchi, David E. Muirhead, Daniel E. Michele, Steven A. Moore, Katsuya Miyake, Paul L. McNeil, Rainer Ng, Susan T. Iannaccone, Erik P. Rader, Michael B. A. Oldstone |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
musculoskeletal diseases
Integrins congenital hereditary and neonatal diseases and abnormalities Glycosylation animal structures Integrin Basement Membrane Dystroglycans Mice Sarcolemma Laminin Dystroglycan medicine Animals Lymphocytic choriomeningitis virus Binding Sites Multidisciplinary biology Skeletal muscle Biological Sciences Muscular Dystrophy Animal musculoskeletal system Cell biology medicine.anatomical_structure Biochemistry biology.protein Pikachurin Basal lamina tissues |
| Zdroj: | Proceedings of the National Academy of Sciences. 106:12573-12579 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0906545106 |
| Popis: | 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 α-dystroglycan 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 sarcolemmal 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|