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

Renzhi Han; Motoi Kanagawa; Takako Yoshida-Moriguchi; Erik P Rader; Rainer A Ng; Daniel E Michele; David E Muirhead; Stefan Kunz; Steven A Moore; Susan T Iannaccone; Katsuya Miyake; Paul L McNeil; Ulrike Mayer; Michael B. A Oldstone; John A Faulkner; Kevin P Campbell

doi:10.1073/pnas.0906545106

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

Journal article

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

Renzhi Han, Motoi Kanagawa, Takako Yoshida-Moriguchi, Erik P Rader, Rainer A Ng, Daniel E Michele, David E Muirhead, Stefan Kunz, Steven A Moore, Susan T Iannaccone, …

Proceedings of the National Academy of Sciences - PNAS, Vol.106(31), pp.12573-12579

Inaugural Article

08/04/2009

DOI: 10.1073/pnas.0906545106

PMCID: PMC2715328

PMID: 19633189

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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 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.

Biological Sciences

Muscular Dystrophy

glycosylation

membrane damage

dystroglycanopathy

integrin

Details

Title: Subtitle: Basal lamina strengthens cell membrane integrity via the laminin G domain-binding motif of α-dystroglycan
Creators: Renzhi Han - Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, Internal Medicine, and
Motoi Kanagawa - Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, Internal Medicine, and
Takako Yoshida-Moriguchi - Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, Internal Medicine, and
Erik P Rader - Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, Internal Medicine, and
Rainer A Ng - Departments of
Daniel E Michele - Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, Internal Medicine, and
David E Muirhead - Texas Scottish Rite Hospital for Children, Dallas, TX 75219
Stefan Kunz - Departments of
Steven A Moore - Pathology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242
Susan T Iannaccone - Department of Pediatric Neurology, Children's Medical Center, University of Texas Southwestern Medical Center, Dallas, TX 75390
Katsuya Miyake - Institute of Molecular Medicine and Genetics, The Medical College of Georgia, Augusta, GA 30912; and
Paul L McNeil - Department of Cellular Biology and Anatomy
Ulrike Mayer - Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, United Kingdom
Michael B. A Oldstone - Departments of
John A Faulkner - Departments of
Kevin P Campbell - Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, Internal Medicine, and
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.106(31), pp.12573-12579
Series: Inaugural Article
DOI: 10.1073/pnas.0906545106
PMID: 19633189
PMCID: PMC2715328
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 08/04/2009
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute
Record Identifier: 9984020628102771

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