title: Basal lamina strengthens cell membrane integrity via the laminin G domain-binding motif of alpha-dystroglycan.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Physiology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Renzhi
authors.initials: R
authors.lastname: Han
authors.forename: Motoi
authors.initials: M
authors.lastname: Kanagawa
authors.forename: Takako
authors.initials: T
authors.lastname: Yoshida-Moriguchi
authors.forename: Erik P
authors.initials: EP
authors.lastname: Rader
authors.forename: Rainer A
authors.initials: RA
authors.lastname: Ng
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Michele
authors.forename: David E
authors.initials: DE
authors.lastname: Muirhead
authors.forename: Stefan
authors.initials: S
authors.lastname: Kunz
authors.forename: Steven A
authors.initials: SA
authors.lastname: Moore
authors.forename: Susan T
authors.initials: ST
authors.lastname: Iannaccone
authors.forename: Katsuya
authors.initials: K
authors.lastname: Miyake
authors.forename: Paul L
authors.initials: PL
authors.lastname: McNeil
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mayer
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
authors.forename: John A
authors.initials: JA
authors.lastname: Faulkner
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
mesh_terms: 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*
chemical_list: D016023:Integrins; D007797:Laminin; D049030:Dystroglycans; C082908:integrin alpha7beta1