Deficiency of dystrophin-associated proteins: A common mechanism leading to muscle cell necrosis in severe childhood muscular dystrophies

doi:10.1016/0960-8966(93)90002-2

Neuromuscular Disorders

Volume 3, Issue 2, 1993, Pages 109-118

https://doi.org/10.1016/0960-8966(93)90002-2 Get rights and content

Abstract

Dystrophin is a large cytoskeletal protein encoded by the Duchenne muscular dystrophy (DMD) gene. Dystrophin is associated with a large oligomeric complex of sarcolemmal glycoproteins, including the novel laminin-binding glycoprotein called dystroglycan, which provides a linkage to the extracellular matrix. In DMD, the absence of dystrophin leads to a drastic reduction in all of the dystrophin-associated proteins. In severe childhood autosomal recessive muscular dystrophy with DMD-like phenotype (SCARMD), a specific deficiency of the 50 kDa dystrophin-associated glycoprotein is found. Thus, the disruption/dysfunction of the dystrophin-glycoprotein complex due to the deficiency of one or more of the dystrophin-associated proteins is presumed to cause the disruption of the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. This may render muscle cells susceptible to necrosis in two forms of severe childhood muscular dystrophy, DMD and SCARMD.

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Satellite cell self-renewal is a necessary process without which recurrent muscle regeneration would rapidly lead to the depletion of the satellite cell pool. However, the observed reduction in satellite cell number with aging [12] indicates that the satellite cell self-renewal cannot completely balance the chronic loss of myonuclei throughout the lifetime [13]; moreover, satellite cell self-renewal does not appear to be able to compensate for the depletion of the satellite cell pool resulting from continuous activation of muscle repair in degenerative skeletal muscle diseases such as muscular dystrophies [14]. Importantly, besides the pivotal role of these skeletal muscle resident cell precursors, in the last few years it has been established that skeletal muscle repair can efficiently be brought about also by mesenchymal stem cells, derived from bone-marrow or associated to vessels (see Section 3) [15].
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Another complicating feature of muscular dystrophy protein diagnostics are secondary protein deficiencies [3,13]. In DMD/BMD patients, the absence or reduction of dystrophin is often coupled with secondary deficiencies in proteins of the dystrophin–glycoprotein complex DGC [14]. Reductions of one of the sarcoglycans in LGMD patients can be coupled with secondary reductions in dystrophin and/or in the other sarcoglycans of such variable extent that the application of one sarcoglycan antibody is not sufficient to discriminate sarcoglycanopathies from other muscular dystrophies [15].
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Review articleDeficiency of dystrophin-associated proteins: A common mechanism leading to muscle cell necrosis in severe childhood muscular dystrophies

Abstract

Cell

Cell

J Biol Chem

Cell

Cell

FEBS Lett

FEBS Lett

Neuron

Neuromusc Disord

FEBS Lett

Association of dystrophin and an integral membrane glycoprotein

Nature

Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle

Nature

Glycoprotein complex anchoring dystrophin to sarcolemma

J Biochem

Dystrophin-glycoprotein complex is highly enriched in isolated skeletal muscle sarcolemma

J Cell Biol

Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix

Nature

The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle

Nature

Immunostaining of skeletal and cardiac muscle surface membrane with antibody against Duchenne muscular dystrophy peptide

Nature

Immunoelectron microscopic localization of dystrophin in myofibres

Nature

A monoclonal antibody against a synthetic polypeptide fragment of dystrophin (amino acid sequence 215–264)

Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy

N Engl J Med

Analysis of the actin-binding domain of α-actinin by mutagenesis and demonstration that dystrophin contains a functionally homologous domain

J Cell Biol

Dense immunostainings on both neuromuscular and myotendon junctions with an anti-dystrophin monoclonal antibody

Biomed Res

Review article
Deficiency of dystrophin-associated proteins: A common mechanism leading to muscle cell necrosis in severe childhood muscular dystrophies