Basal lamina strengthens cell membrane integrity via the laminin G domain-binding motif of alpha-dystroglycan.
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 alpha7 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.
Han
Renzhi
R
Howard Hughes Medical Institute, Department of Molecular Physiology, The University of Iowa, Iowa City, IA 52242, USA.
Kanagawa
Motoi
M
Yoshida-Moriguchi
Takako
T
Rader
Erik P
EP
Ng
Rainer A
RA
Michele
Daniel E
DE
Muirhead
David E
DE
Kunz
Stefan
S
Moore
Steven A
SA
Iannaccone
Susan T
ST
Miyake
Katsuya
K
McNeil
Paul L
PL
Mayer
Ulrike
U
Oldstone
Michael B A
MB
Faulkner
John A
JA
Campbell
Kevin P
KP
D000818:Animals; D001485:Basement Membrane / Q000502:physiology*; D001665:Binding Sites; D049030:Dystroglycans / Q000737:chemistry / Q000502:physiology*; D006031:Glycosylation; D016023:Integrins / Q000502:physiology; D007797:Laminin / Q000737:chemistry / Q000502:physiology*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D009137:Muscular Dystrophy, Animal / Q000209:etiology; D012508:Sarcolemma / Q000502:physiology*
D016023:Integrins; D007797:Laminin; D049030:Dystroglycans; C082908:integrin alpha7beta1