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

R Han, M Kanagawa… - Proceedings of the …, 2009 - National Acad Sciences
R Han, M Kanagawa, T Yoshida-Moriguchi, EP Rader, RA Ng, DE Michele, DE Muirhead…
Proceedings of the National Academy of Sciences, 2009National Acad Sciences
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 …
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 Largemyd 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 Largemyd 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.
National Acad Sciences