Dystrophic phenotype induced in vitro by antibody blockade of muscle alpha-dystroglycan-laminin interaction

Susan C Brown; Ariberto Fassati; Linda Popplewell; Anton M Page; Michael D Henry; Kevin P Campbell; George Dickson

doi:10.1242/jcs.112.2.209

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Dystrophic phenotype induced in vitro by antibody blockade of muscle alpha-dystroglycan-laminin interaction

Journal article

Peer reviewed

Dystrophic phenotype induced in vitro by antibody blockade of muscle alpha-dystroglycan-laminin interaction

Susan C Brown, Ariberto Fassati, Linda Popplewell, Anton M Page, Michael D Henry, Kevin P Campbell and George Dickson

Journal of cell science, Vol.112(2), pp.209-216

01/1999

DOI: 10.1242/jcs.112.2.209

PMID: 9858474

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https://research.tees.ac.uk/en/publications/6656f792-76e3-40a9-a976-3493d5287f8bView

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Abstract

alpha-dystroglycan is a glycoprotein expressed on the surface of skeletal muscle fibres and other cell types. In muscle, alpha-dystroglycan provides a link between the myofibre cytoskeleton through its indirect binding to dystrophin, and the basal lamina through its binding to laminin-2, a protein of the extracellular matrix. The disruption of this linkage between the myofibre cytoskeleton and the extracellular matrix is a common feature of Duchenne and other muscular dystrophies, though the pathogenic mechanisms leading to muscle wasting remain unknown. By treating primary mouse muscle cultures with a monoclonal antibody which blocks alpha-dystroglycan binding to laminin, we show here the induction of a dystrophic phenotype in vitro. The phenotype is inducible in differentiated cultures only, is characterised by reduced myotube size, myofibril disorganisation, loss of contractile activity, reduced spontaneous clustering of acetylcholine receptors and is reversed by addition of excess exogenous laminin-2. Thus, alpha-dystroglycan may be part of a signalling pathway for the maturation and maintenance of skeletal myofibres. Detailed knowledge of this signalling pathway may provide insights into the molecular pathology of the various inherited muscular dystrophies, and identify valuable pharmacological targets and new therapeutic strategies.

Cell Differentiation

Phenotype

Cytoskeletal Proteins - antagonists & inhibitors

Membrane Glycoproteins - metabolism

Antibodies, Monoclonal - pharmacology

Cells, Cultured

Laminin - antagonists & inhibitors

Muscle, Skeletal - ultrastructure

Muscle, Skeletal - metabolism

Microscopy, Electron

Dystroglycans

Muscular Dystrophy, Animal - pathology

Cell Fusion

Animals

Cytoskeletal Proteins - immunology

Membrane Glycoproteins - antagonists & inhibitors

Muscular Dystrophy, Animal - etiology

Muscular Dystrophy, Animal - metabolism

Protein Binding

Cytoskeletal Proteins - metabolism

Mice

Laminin - metabolism

Membrane Glycoproteins - immunology

Laminin - immunology

Details

Title: Subtitle: Dystrophic phenotype induced in vitro by antibody blockade of muscle alpha-dystroglycan-laminin interaction
Creators: Susan C Brown - Division of Biochemistry, School of Biological Sciences, Royal Holloway College, University of London, Egham, Surrey TW20 0EX, UK
Ariberto Fassati
Linda Popplewell
Anton M Page
Michael D Henry
Kevin P Campbell
George Dickson
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.112(2), pp.209-216
DOI: 10.1242/jcs.112.2.209
PMID: 9858474
NLM abbreviation: J Cell Sci
ISSN: 0021-9533
eISSN: 1477-9137
Publisher: England
Grant note: Wellcome Trust
Language: English
Date published: 01/1999
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Radiation Oncology; Urology
Record Identifier: 9984068370102771

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